John Garner's Technical Blog
John GarnerJohn Garner, Manager

What's New and on the Manager's Mind

A blog dedicated to answering technical questions in an open format relating to products from PolySciTech, a division of Akina, Inc.


Select a topic to hide all other entries.
The most recent item is at the top.

Fluorescent-PLGA and PLGA-PEG-Mal from PolySciTech used in study on Fab-targeting of nanoparticles

Monday, March 19, 2018, 6:27 PM ET

Targeted nanoparticles have come to the forefront recently for their application towards cancer by allowing the particles to bind to specific sites on tumors. There are many factors, however, which can interfere with this process and not all of them are well understood yet. Recently, researchers at Universidade do Porto (Portugal) and Uppsala University (Sweden) utilized fluorescently-tagged PLGA (PLGA-FKR648, AV015) and PLGA-PEG-Mal (AI110) from PolySciTech (www.polyscitech.com) to create Fab-decorated nanoparticles bearing a fluorescent tracer. These particles were used, along with a series of surfactants, to determine the impact these surfactants had on the targeting capabilities of these nanoparticles. This research holds promise to help in generation of more effective targeted nanoparticle systems by optimizing the surfactant utilized. Read more: Kennedy, Patrick J., Ines Perreira, Daniel Ferreira, Marika Nestor, Carla Oliveira, Pedro L. Granja, and Bruno Sarmento. "Impact of Surfactants on the Target Recognition of Fab-Conjugated PLGA Nanoparticles." European Journal of Pharmaceutics and Biopharmaceutics (2018). https://www.sciencedirect.com/science/article/pii/S0939641118301784

“Abstract: Targeted drug delivery with nanoparticles (NPs) requires proper surface ligand presentation and availability. Surfactants are often used as stabilizers in the production of targeted NPs. Here, we evaluated the impact of surfactants on ligand functionalization and downstream molecular recognition. Our model system consisted of fluorescent poly(lactic-co-glycolic acid) (PLGA) NPs that were nanoprecipitated in one of a small panel of commonly-used surfactants followed by equivalent washes and conjugation of an engineered Fab antibody fragment. Size, polydispersity index and zeta potential were determined by dynamic light scattering and laser Doppler anemometry, and Fab presence on the NPs was assessed by enzyme-linked immunosorbent assay. Most importantly, Fab-decorated NP binding to the cell surface receptor was monitored by fluorescence-activated cell sorting. 2% polyvinyl alcohol, 1% sodium cholate, 0.5% Pluronic F127 (F127) and 2% Tween-80 were initially tested. Of the four surfactants tested, PLGA NPs in 0.5% F127 and 2% Tween-80 had the highest cell binding. These two surfactants were then retested in two different concentrations, 0.5% and 2%. The Fab-decorated PLGA NPs in 2% F127 had the highest cell binding. This study highlights the impact of common surfactants and their concentrations on the downstream targeting of ligand-decorated NPs. Similar principles should be applied in the development of future targeted nanosystems where surfactants are employed. Keywords: Targeted nanoparticles; PLGA nanoparticles; surfactant; Fab antibody fragment”

BPCR conference (August 29, 2018 9AM - 4PM: Kurz Purdue Technology Center, West Lafayette, IN) is a free, 1-day scientific networking conference hosted by Akina, Inc. which focuses on research companies in the biotechnology, pharmaceutical, medical, and broader life-science fields. See more at BPCRconference.com

Maleimide-PEG-PLGA from PolySciTech used in fundamental research on thiol-maleimide conjugation for generating targeted nanoparticles

Thursday, March 15, 2018, 9:18 PM ET

A popular method for cancer treatment is to apply chemotherapeutic or other agents through nanoparticles that float through the patient’s bloodstream. Ideally, these particles are preferentially retained within the tumor site where they deliver their medicinal payload. To facilitate this, the nanoparticles are often covered with a specific targeting ligand. This ligand binds to a select site present on the cancer cells which is not found, or is less prevalent in, normal tissue. A popular chemical technique to create such a nanoparticle is to use PLGA-PEG-Maleimide as a precursor component for making nanoparticles covered with maleimide groups. These maleimides react readily with thiols (typically found in proteins as cysteine units) to bind the protein ligand to the outer surface of the nanoparticle. Despite this reaction’s popularity for use in generating targeted nanoparticles, little has been done in terms of understanding and optimizing the exact reaction kinetics involved with this reaction. Recently, researchers at Utrecht University (Netherlands) utilized reactive maleimide-PEG-PLGA (AI020) and inert methoxy-PEG-PLGA (AK037) from PolySciTech (www.polyscitech.com) to investigate the reaction kinetics and optimization parameters of thiol-maleimide conjugation as applied to nanoparticles. Notably, they found that the formed maleimide-coated nanoparticles should be used soon after manufacture as the maleimide unit itself can be affected by a hydrolysis reaction. This valuable research provides critical information for researchers looking to design targeted nanoparticles using this popular and robust chemistry. Read more: Martínez-Jothar, Lucía, Sofia Doulkeridou, Raymond M. Schiffelers, Javier Sastre Torano, Sabrina Oliveira, Cornelus F. van Nostrum, and Wim E. Hennink. "Insights into maleimide–thiol conjugation chemistry: conditions for efficient surface functionalization of nanoparticles for receptor targeting." Journal of Controlled Release (2018). https://www.sciencedirect.com/science/article/pii/S0168365918301238

“Abstract: Maleimide-thiol chemistry is widely used for the design and preparation of ligand-decorated drug delivery systems such as poly(lactide-co-glycolide) (PLGA) based nanoparticles (NPs). While many publications on nanocarriers functionalized exploiting this strategy are available in the literature, the conditions at which this reaction takes place vary among publications. This paper presents a comprehensive study on the conjugation of the peptide cRGDfK and the nanobody 11A4 (both containing a free thiol group) to maleimide functionalized PLGA NPs by means of the maleimide-thiol click reaction. The influence of different parameters, such as the nanoparticles preparation method and storage conditions as well as the molar ratio of maleimide to ligand used for conjugation, on the reaction efficiency has been evaluated. The NPs were prepared by a single or double emulsion method using different types and concentrations of surfactants and stored at 4 or 20 °C before reaction with the targeting moieties. Several maleimide to ligand molar ratios and different reaction times were studied and the conjugation efficiency was determined by quantification of the not-bound ligand by liquid chromatography. The kind of emulsion used to prepare the NPs as well as the type and concentration of surfactant used had no effect on the conjugation efficiency. Reaction between the maleimide groups present in the NPs and cRGDfK was optimal at a maleimide to thiol molar ratio of 2:1, reaching a conjugation efficiency of 84 ± 4% after 30 min at room temperature in 10 mM HEPES pH 7.0. For 11A4 nanobody the optimal reaction efficiency, 58 ± 12%, was achieved after 2 h of incubation at room temperature in PBS pH 7.4 using a 5:1 maleimide to protein molar ratio. Storage of the NPs at 4 °C for 7 days prior to their exposure to the ligands resulted in approximately 10% decrease in the reactivity of maleimide in contrast to storage at 20 °C which led to almost 40% of the maleimide being unreactive after the same storage time. Our findings demonstrate that optimization of this reaction, particularly in terms of reactant ratios, can represent a significant increase in the conjugation efficiency and prevent considerable waste of resources. Keywords: Nanoparticles; PLGA; Maleimide; Targeting; RGD; Nanobody”

BPCR conference (August 29, 2018 9AM - 4PM: Kurz Purdue Technology Center, West Lafayette, IN) is a free, 1-day scientific networking conference hosted by Akina, Inc. which focuses on research companies in the biotechnology, pharmaceutical, medical, and broader life-science fields. See more at BPCRconference.com

PLLA from PolySciTech used in fundamental research project on polymer processing conditions and crystallinity formation

Monday, March 12, 2018, 5:47 PM ET

One of the key parameters controlling polymer mechanical and optical behavior is how the polymer chains arrange or ‘stack’ relative to each other. Chemically, polymers with regular, repeating structures tend to stack more closely into crystalline forms than polymers which have irregular structures where steric hindrance prevent the chains from getting to close to one another. Additionally, the speed and conditions at which the polymers solidify (either from solvent or melt) as well as any mechanical drawing force play a role in crystalline domain formation. The more time the chains have to rearrange, the more they tend to crystallize and, if there is an applied force, they tend to crystallize parallel to the direction of the force. Recently, researchers from Université d’Orléans (France) utilized PLLA (PolyVivo AP006 and PolyVivo AP050) from PolySciTech (www.polyscitech.com) to perform fundamental research on the effect processing conditions have on crystalline PLLA film formation. This research holds promise for the development of mechanically robust or optically clear components for use in biomedical applications. Read more: Vayer, Marylène, Alain Pineau, Fabienne Warmont, Marjorie Roulet, and Christophe Sinturel. "Constrained crystallization of poly (L-lactic acid) in thin films prepared by dip coating." European Polymer Journal (2018)., https://www.sciencedirect.com/science/article/pii/S0014305717322413

“Abstract: Dip coating process used at various withdrawing speeds showed a great ability to control the crystalline structure of thin films of poly(L-lactic acid) which can be of great importance for applications where mechanical or optical properties are involved. Thin films were studied by Atomic Force Microscopy and Grazing Incidence Angle X-ray Diffraction. Withdrawing the silicon substrate in the draining regime (at high speed) led to amorphous films with flat surface whatever the solvent and the molar mass. At low speeds (capillary regime), AFM demonstrated the presence of spherulites or hedrites in the films depending on the solvent and the molar mass. GIXRD showed that spherulites were less crystallized than hedrites. This difference was attributed to solvent evaporation rate. Highlights: PLLA thin films were prepared by dip coating solutions. The thin films were investigated using AFM and GIXRD. Withdrawal at high speed led to amorphous films. Withdrawal at low speed led to partially crystallized films. The nature of solvent and molecular mass influenced the crystalline structure of the films.”

PLGA-PEG-COOH from PolySciTech used in the development of Salinomycin-loaded nanoparticle-based ovarian cancer treatment

Tuesday, March 6, 2018, 9:26 PM ET

Like other tissues, cancer has stem cells as part of its growth. In the case of cancer, these stem cells serve to allow the disease to regrow even if the main tumor is destroyed by traditional therapy. One therapeutic approach is to target the stem-cells thus preventing cancer from re-growing. Recently, researchers at Hubei University of Medicine and Wuhan University (China) used PLGA-PEG-COOH (PolyVivo AI034) from PolySciTech (www.polyscitech.com) to generate CD133 targeted nanoparticles for delivering Salinomycin to ovarian cancer stem cells. This research holds promise for improved therapeutic strategies for this potentially fatal form of cancer. Read more: Mi, Yi, Yuqin Huang, and Jie Deng “The enhanced delivery of salinomycin to CD133+ ovarian cancer stem cells through CD133 antibody conjugation with poly(lactic-co-glycolic acid)-poly(ethylene glycol) nanoparticles” Oncology Letters 2018, DOI: 10.3892/ol.2018.8140 https://www.spandidos-publications.com/10.3892/ol.2018.8140

“Abstract: Ovarian cancer is the most lethal gynecologic malignancy, and ovarian cancer stem cells (CSCs) serve a pivotal function in the metastasis and recurrence of ovarian cancer. Multiple previous studies have validated CD133 as a marker of ovarian CSCs. Although salinomycin is a promising therapeutic agent that has been demonstrated to kill CSCs in various types of cancer, poor aqueous solubility hampers its clinical application. The present study used salinomycinloaded poly(lacticcoglycolic acid)poly(ethylene glycol) nanoparticles conjugated with CD133 antibodies (CD133SALNP) to eliminate CD133+ ovarian CSCs. The results revealed that CD133SALNPs were of an appropriate size (149.2 nm) and exhibited sustained drug release. CD133SALNPs efficiently bound to CD133+ ovarian cancer cells, resulting in an increased cytotoxic effect in CD133+ ovarian cancer cells, compared with the untargeted SALNPs and salinomycin. CD133SALNPs reduced the percentage of CD133+ ovarian CSCs in ovarian cells more effectively than treatment with salinomycin or SALNPs, suggesting that CD133SALNP targeted CD133+ ovarian CSCs. In nude mice bearing ovarian cancer xenografts, CD133SALNPs exerted improved therapeutic effects compared with SALNPs and salinomycin. Thus, CD133 was demonstrated to be a promising target for drug delivery to ovarian CSCs, and may be useful as an agent to inhibit the growth of ovarian cancer by targeting CD133+ ovarian CSCs. CD133SALNPs may therefore represent a promising approach for the treatment of ovarian cancer.”

PLA-PEG-PLA from PolySciTech used in development of Photo-thermal platform for use in post-surgical treatment of cancer

Tuesday, March 6, 2018, 9:25 PM ET

There are many different types of ‘light’ beyond the visible spectrum. One example is near-infrared (~700-1000 nm), which is of lower frequency than visible red light. This form of light has the unique capability to penetrate through tissue. This feature is typically applied in tandem with a fluorescent dye for imaging, however it can also be applied with a photothermal agent to cause localized heating in a specific region, such as the tissue immediately surrounding a tumor. Recently, researchers at the Chinese Academy of Sciences and the City University of Hong Kong used PLA-PEG-PLA thermogel (Polyvivo AK100) from PolySciTech (www.polyscitech.com) to generate a near-infrared responsive photothermal therapy gel system. This research holds promise for the development of novel therapeutic options for cancer treatment. Read more: Shao, Jundong, Changshun Ruan, Hanhan Xie, Zhibin Li, Huaiyu Wang, Paul K. Chu, and Xue-Feng Yu “Black-Phosphorus-Incorporated Hydrogel as a Sprayable and Biodegradable Photothermal Platform for Postsurgical Treatment of Cancer” Adv. Sci. 2018, 1700848, 3 March 2018, 10.1002/advs.201700848 http://onlinelibrary.wiley.com/doi/10.1002/advs.201700848/full

“Abstract: Photothermal therapy (PTT) is a fledgling therapeutic strategy for cancer treatment with minimal invasiveness but clinical adoption has been stifled by concerns such as insufficient biodegradability of the PTT agents and lack of an efficient delivery system. Here, black phosphorus (BP) nanosheets are incorporated with a thermosensitive hydrogel [poly(d,l-lactide)-poly(ethylene glycol)-poly(d,l-lactide) (PDLLA-PEG-PDLLA: PLEL)] to produce a new PTT system for postoperative treatment of cancer. The BP@PLEL hydrogel exhibits excellent near infrared (NIR) photothermal performance and a rapid NIR-induced sol–gel transition as well as good biodegradability and biocompatibility in vitro and in vivo. Based on these merits, an in vivo PTT postoperative treatment strategy is established. Under NIR irradiation, the sprayed BP@PLEL hydrogel enables rapid gelation forming a gelled membrane on wounds and offers high PTT efficacy to eliminate residual tumor tissues after tumor removal surgery. Furthermore, the good photothermal antibacterial performance prevents infection and this efficient and biodegradable PTT system is very promising in postoperative treatment of cancer.”

Akina, Inc. hosting free scientific-networking conference in West Lafayette Purdue Research Park on August 29

Monday, March 5, 2018, 10:09 AM ET

Thanks to the efforts of numerous entrepreneurs, working alongside Purdue Research Foundation, the number of scientific and engineering startup companies in the West Lafayette has exploded over the past decade. In order to encourage collaborations, networking, and visibility in the biotechnology, pharmaceutical, and research-oriented fields, Akina, Inc. (www.akinainc.com) is hosting the BPCR Conference. This is a free, 1-day scientific-networking conference located at the Kurz Purdue Technology Center (KPTC), right in the heart of the Purdue Research Park, and is open to the public. Booth space (10x10’, includes 6’ table and 2 chairs) as well as ‘soap-box’ presentations (30 min. Audio-visual support provided) slots are still available, but will fill up fast so plan to register sooner rather than later. Lunch is provided for registered attendees. Learn more and register online at BPCRconference.com

mPEG-PLA from PolySciTech used in development of novel quisinostat-loaded nanoparticles for brain-cancer therapy

Wednesday, February 28, 2018, 1:51 PM ET

DNA in human cells can be either loose or tightly bound to proteins known as histones. When DNA is bound to histones, it cannot be transcribed (read) and this is a typical method of gene control within a cell as only the relevant portions of the DNA can be transcribed. Unlike normal cells, fast-growing cancers have an excess of an enzyme which binds DNA to the histones very tightly and affects how it is read changing how the cells DNA is interpreted. It has been found that inhibitors of this enzyme, such as quisinostat, can prevent the growth and spread of certain cancers. However, these inhibitors have very poor uptake and delivery. Recently, researchers at Barrow Neurological Institute and Arizona State University utilized mPEG-PLA (polyvivo AK054) from PolySciTech (www.polyscitech.com) to generate nanoparticles loaded with quisinostat. They found these nanoparticles to be effective in slowing the growth of glioblastoma in an animal model. This research holds promise for developing new therapeutic strategies for rapidly growing cancers including brain-cancer. Read more: Householder, Kyle T., Danielle M. DiPerna, Eugene P. Chung, Rosa Luning, Duong Nguyen, Sarah Stabenfeldt, Shwetal Mehta, and Rachael W. Sirianni. "pH Driven Precipitation of Quisinostat onto PLA-PEG Nanoparticles Enables Treatment of Intracranial Glioblastoma." Colloids and Surfaces B: Biointerfaces (2018). https://www.sciencedirect.com/science/article/pii/S0927776518301231

“Highlights: Ionized quisinostat is loaded more efficiently onto PLA-PEG nanoparticles. Quisinostat potency is maintained through nanoparticle processing. Quisinostat-loaded nanoparticles administered IV slow intracranial GL261 glioma tumors. Abstract: Histone deacetylases (HDACs) are known to be key enzymes in cancer development and progression through their modulation of chromatin structure and numerous proteins. Aggressive dedifferentiated tumors, like glioblastoma, frequently overexpress HDACs, while HDAC inhibition can lead to cell cycle arrest, promote cellular differentiation and induce apoptosis. Although multiple HDAC inhibitors, such as quisinostat, are of interest in oncology therapy due to their potent in vitro efficacy, poor delivery has been attributed to their failure in the clinic as monotherapies against solid tumors. Thus, we were motivated to develop quisinostat loaded poly(D,L-lactide)-b-methoxy poly(ethylene glycol) nanoparticles (NPs) to test their ability to enable effective quisinostat delivery to orthotopic glioblastoma. In developing our NP formulation, we identified a novel, pH-driven approach for achieving over 9% (w/w) quisinostat loading. We show quisinostat-loaded NPs maintain drug potency in vitro and effectively slow tumor growth in vivo, leading to a prolonged survival compared to control mice. Keywords: Glioblastoma; nanoparticle; HDAC; quisinostat (JNJ-26481585); PLA-PEG; pH”

PLGA-PEG-NHS and mPEG-PLGA from PolySciTech used in development of peptide-targeting nanoparticle for triple-negative breast cancer therapy

Monday, February 19, 2018, 5:24 PM ET

Targeted medicine is better described as ‘retentive’ or possibly ‘adhesive’ medicine. Any molecule which enters the human blood-stream is rapidly circulated throughout all parts of the entire body. Conventional medicines have a very limited and specific mechanism of action, which is why their effects are only experienced in the disease-state locations. That being said, exceeding the dosage on conventional drugs can cause toxic effects and the most common example of this is acetaminophen, a headache medicine, which in excessive doses can cause toxicity in the liver. Amongst medicinal therapies, chemotherapy is unique in that it is comprised of compounds known to either kill, or prevent the replication of, human cells and it is dosed at a concentration known to be toxic. The ‘theory of action’ is that, since the cancer is growing faster than all other tissues, it will be more affected than other tissues. Unfortunately, all cells are affected, which is why chemotherapy patients lose their hair and have several other side-effects. Although medicine in the blood-stream will flow to all parts of the human body, use of nanoparticles or other delivery systems which have a specific binding ligand will encourage the nanoparticles to be retained at the site of specific cells through ligand binding mechanisms (e.g. the nanoparticles flow everywhere, but they ‘stick’ to the cancer by ligand binding) Recently, researchers from Johns Hopkins University and AsclepiX Therapeutics used AI111 (PLGA-PEG-NHS) and AK037 (mPEG-PLGA) from PolySciTech (www.polyscitech.com) to create peptide-decorated nanoparticles for adhesion to triple-negative breast cancer. This research holds promise for improved treatments for this drug-resistant and highly invasive form of cancer. Read more: Bressler, Eric M., Jayoung Kim, Ron B. Shmueli, Adam C. Mirando, Hojjat Bazzazi, Esak Lee, Aleksander S. Popel, Niranjan B. Pandey, and Jordan J. Green. "Biomimetic peptide display from a polymeric nanoparticle surface for targeting and antitumor activity to human triple‐negative breast cancer cells." Journal of Biomedical Materials Research Part A (2018). http://onlinelibrary.wiley.com/doi/10.1002/jbm.a.36360/full

“Abstract: While poly(lactic-co-glycolic acid)-block-polyethylene glycol (PLGA-PEG) nanoparticles (NPs) can encapsulate drug cargos and prolong circulation times, they show non-specific accumulation in off-target tissues. Targeted delivery of drugs to tumor tissue and tumor vasculature is a promising approach for treating solid tumors while enhancing specificity and reducing systemic toxicity. AXT050, a collagen-IV derived peptide with both antitumor and antiangiogenic properties, is shown to bind to tumor-associated integrins with high affinity, which leads to targeted accumulation in tumor tissue. AXT050 conjugated to PLGA-PEG NPs at precisely controlled surface density functions both as a targeting agent to human tumor cells and demonstrates potential for simultaneous antitumorigenic and antiangiogenic activity. These targeted NPs cause inhibition of adhesion and proliferation in vitro when added to human triple-negative breast cancer cells and microvascular endothelial cells through binding to integrin αVβ3. Furthermore, we find an in vivo biphasic relationship between tumor targeting and surface coating density of NPs coated with AXT050. NPs with an intermediate level of 10% peptide surface coating show approximately two-fold greater accumulation in tumors and lower accumulation in the liver compared to non-targeted PLGA-PEG NPs in a murine biodistribution model. Display of biomimetic peptides from NP surfaces to both target and inhibit cancer cells has the potential to enhance the activity of cancer nanomedicines.”

Mal-PEG-PLGA and mPEG-PLGA from PolySciTech used to develop phototherapy nanoparticles for triple-negative breast cancer treatment

Thursday, February 15, 2018, 4:11 PM ET

Cancer survival rates and prognosis depends on both location and type of cancer. For breast-cancer, one of the most devastating and difficult to treat forms is what is referred to as triple-negative breast cancer. This breast cancer lacks typical markers and factors, such as HER, which normal breast cancers possess. Since these markers are usually targeted in traditional therapy, this makes treating this type of cancer very difficult. Additionally, these types of cancer tend to grow aggressively. Recently, researchers from University of Massachusetts Lowell used Polyvivo mPEG-PLGA (AK037) and PLGA-PEG-Mal (AI020) from PolySciTech (www.polyscitech.com) to develop unique phototriggered nanoparticles to treat breast cancer which respond to near-infrared light to destroy the tumors. This holds promise for improved treatment options for this often lethal and difficult to treat disease. Read more: Jadia, Rahul, Janel Kydd, and Prakash Rai. "Remotely Phototriggered, Transferrin‐Targeted Polymeric Nanoparticles for the Treatment of Breast Cancer." Photochemistry and Photobiology. http://onlinelibrary.wiley.com/doi/10.1111/php.12903/full

“Abstract: Triple Negative Breast Cancer (TNBC) has the worst prognosis amongst all sub-types of breast cancer. Currently no targeted treatment has been approved for TNBC. The goal of this study was to design a remotely triggered, targeted therapy for TNBC using polymeric nanoparticles and light. Active targeting of TNBC was achieved by conjugating the nanoparticles to a peptide (hTf) that binds to the transferrin receptor, which is overexpressed in TNBC. Photodynamic Therapy (PDT) was explored for TNBC treatment by remotely triggering benzoporphyrin derivative monoacid (BPD), a photosensitizer, using near infrared light. In this study, we investigated the use of actively targeting polymeric nanoparticles for PDT against TNBC using in vitro imaging and cytotoxicity studies. Fluorescence imaging confirmed that the BPD loaded nanoparticles showed greater fluorescence in TNBC cells compared to free BPD, but more importantly actively targeted nanoparticles displayed stronger fluorescence compared to passively targeted nanoparticles. Moreover, fluorescence imaging following competition with empty targeted nanoparticles validated the specificity of the targeted nanoparticles for TNBC cells. The PDT killing results were in line with the fluorescence imaging results, where actively targeting nanoparticles exhibited the highest phototriggered cytotoxicity in TNBC cells, making them an attractive nanoplatform for TNBC treatment.”

PLLA from PolySciTech used in developing bioscaffold with dedicated perfusion channel for improved cell-growth

Thursday, February 15, 2018, 4:10 PM ET

Tissue engineering is a new field which holds promise to replace damaged or missing bone, muscle, skin, and even nerve tissue in injured patients. This technology relies on use of cell-scaffolds to provide mechanical support to the growing cells, as well as maintain suitable oxygen perfusion, cell-compatibility, and blood flow. This technology holds amazing potential to prevent amputations or life-time paralysis in the wake of severe trauma. However, the exact structure and nature of the cell-scaffold has to be exactly designed in order for the new-growing tissue to succeed. Recently, researchers at Chonnam National University (Korea) used PLLA (PolyVivo AP007) from PolySciTech (www.polyscitech.com) to develop a novel bone-tissue scaffold with a dedicated perfusion channel to ensure flow of oxygenated blood to the growing cells. This research holds promise to provide for repairing or replacing severely damaged bone tissue without requiring an autograft. Read more: Tan, Shiyi, Jiafei Gu, Seung Chul Han, Dong-Weon Lee, and Kiju Kang. "Design and fabrication of a non-clogging scaffold composed of semi-permeable membrane." Materials & Design 142 (2018): 229-239. https://www.sciencedirect.com/science/article/pii/S0264127518300418

“Highlights: A 3D polymer membrane architecture was proposed as a novel concept of bio scaffold. It had two sub-volumes that were intertwined but separated by a semi-permeable membrane. One sub-volume was used for cell culture, while the other served as a perfusion channel. Mass transfer was implemented through the interfacial semi-permeable membrane. Despite very high porosity, its strength & modulus was appropriate for bones or cartilages. Abstract: In this study, a novel concept of polymer scaffold was proposed based on 3D porous membrane architecture. It had two distinct sub-volumes intertwined with each other but separated by a single continuous smooth semi-permeable membrane. One sub-volume was used for cell culture, while the other served as a perfusion channel. Mass transfer was implemented through the interfacial porous membrane. Consequently, this scaffold was expected to be completely free from clogging problem due to growing tissue. The sample scaffolds of poly l-lactic acid (PLLA) was fabricated based on 3D UV photo-lithography and porogen leaching technique, which provided a P-surface-like architecture composed of porous membrane having smooth and fine texture with considerably high porosity. Despite high overall porosity of approximately 97%, these scaffolds had strengths and Young's moduli appropriate for regeneration of bones or cartilages. Wettability and permeability of polydopamine-coated PLLA porous membrane were sufficiently high. Keywords: 3D membrane architecture; Minimal surface; Scaffold; 3D lithography”

PLGA, PLA, and PCL from PolySciTech used in fundamental research on Penicillin depot delivery

Thursday, February 15, 2018, 4:10 PM ET

There is great value in research for not only publishing results from successes but also from publishing results from lessons learned along the way (so-called ‘Negative results’). PLGA is a widely used polymer but its biodegradation naturally leads to formation of acidic products. These products (lactic/glycolic acid) are biocompatible, as they are common metabolic products already formed during normal cellular metabolism. However, they are still acidic in nature and can lead to a drop in pH within the PLGA carrier (For more on this, check out https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4269251/). Penicillin is a widely used antibiotic that is also effective at treating rheumatic heart disease when applied as a series of injections. Recently, Researchers from Monash University, The University of Western Australia, and Princess Margaret Hospital for Children (Australia) used a variety of PLGA’s. PLA’s, and PCL polymers from PolySciTech (www.polyscitech.com) as part of a study on penicillin delivery. This included PolyVivo PLGA’s (AP021, AP043, and AP039) and PolyVivo PLA (AP071) as well as other polymers from PolySciTech to develop an injectable depot formulation for penicillin based on biocompatible NMP solvent. They discovered that the acid-sensitive nature of penicillin, however, prevented it from being used with PLGA as a carrier as the lactic/glycolic acid components degraded the penicillin. Use of PCL fixed this issue, however the total implant mass required an unwieldly 7 grams of material. This research provides critical understanding for others looking to develop long-acting injectable formulations. Read more: Montagnat, Oliver D., Graham R. Webster, Jurgen Bullita, Cornelia Landersdorfer, Rosemary Wyber, Meru Sheel, Jonathan R. Carapetis, and Ben J. Boyd. "Lessons learned in the development of sustained release penicillin drug delivery systems for the prophylactic treatment of rheumatic heart disease (RHD)." Drug Delivery and Translational Research (2018): 1-11. https://link.springer.com/article/10.1007/s13346-018-0482-z

“Abstract: The current prophylactic treatment to prevent rheumatic heart disease requires four-weekly intramuscular injection of a suspension of the poorly soluble benzathine salt form of penicillin G (BPG) often for more than 10 years. In seeking to reduce the frequency of administration to improve adherence, biodegradable polymer matrices have been investigated. Poly(lactide-co-glycolide) (PLGA)-based in situ forming precursor systems containing N-methyl-2-pyrrolidone as solvent and PLGA-based monolithic implants for surgical implantation containing BPG were developed. Long-term release studies indicated low and plateaued release of penicillin G, but continual favourable release profiles for the benzathine counterion, indicating degradation of the polymer and generation of acidic microenvironment being detrimental to penicillin stability. In order to avoid the issue of the acidic product, poly(caprolactone)(PCL) implants were also investigated, with favourable penicillin G release behaviour being achieved, and slow release over 180 days. However, when taking into account the mass of polymer, and the total dose of drug calculated from literature pharmacokinetic parameters for penicillin G, we concluded that an implant size of over 7 g would still be required. This may preclude clinical deployment of a polymer matrix type delivery system for this indication in children and adolescents. Therefore, we have learned that biodegradable PLGA-type systems are not suitable for development of sustained release BPG treatments and that although the PCL system provides favourable release behaviour, the total size of the implant may still present a hurdle for future development. Keywords Rheumatic fever Antibiotic Sustained release Drug delivery PLGA Therapeutic implant”

PLGA from PolySciTech used in the development of a multi-functional, theranostic nanoparticle for cancer therapy

Saturday, February 10, 2018, 10:24 PM ET

“Theranostic” is a term which combines ‘therapy’ and ‘diagnostic’ into a single word. In the realm of cancer research, it is a highly-sought after property for any regimen as cancer is difficult to diagnose, locate, and treat. Nanoparticles which can be targeted towards the cancerous lesions and render them either visible or act as ultrasound/electromagnetic contrast agents have great value in locating and diagnosing the cancer while nanoparticles which deliver chemotherapeutic agents can be useful for treating cancer. Recently, researchers working jointly at Yangzhou University and Soochow University (China) used PLGA (AP040) from PolySciTech (www.polyscitech.com) to develop nanoparticles which were decorated with gold nanoparticles (act as contrast agents as well as photosensitizers) and were loaded with doxorubicin (a chemotherapeutic agent). These particles were tested and found to be effective both at locating cancer as well as treating it. This research holds promise to provide for both improved diagnosis and treatment of cancer. Read more: Xi, Juqun, Wenjuan Wang, Lanyue Da, Jingjing Zhang, Lei Fan, and Lizeng Gao. "Au-PLGA hybrid nanoparticles with catalase-mimicking and near-infrared photothermal activities for photoacoustic imaging-guided cancer therapy." ACS Biomaterials Science & Engineering (2018). http://pubs.acs.org/doi/abs/10.1021/acsbiomaterials.7b00901

“Imaging-guided diagnosis and therapy has been highlighted in the area of nanomedicines. However, integrating multiple functions with high performance in one theranostic (“all-in-one”) still presents considerable challenges. Here, “all-in-one” nanoparticles with drug-loading capacity, catalase-mimetic activity, photoacoustic (PA) imaging ability and photothermal properties were prepared by decorating Au nanoparticles on doxorubicin (DOX) encapsulated poly(lactic-co-glycolic acid) (PLGA) vehicle. The results revealed that the as-prepared Au-PLGA hybrid nanoparticles possessed high photothermal conversion efficiency of up to approximately 69.0%, meanwhile their strong acoustic generation endowed them with efficient PA signal sensing for cancer diagnosis. On an 808 nm laser irradiation, the O2 generation, DOX release profile and reactive oxygen species (ROS) level were all improved, which were beneficial to relieving tumor hypoxia and enhanced the cancer chemo/PTT combined therapy. Overall, the multifunctional Au-PLGA hybrid nanoparticles with these integrated advantages shows promise in PA imaging-guided diagnosis and synergistic tumor ablation. Keywords: Au-PLGA hybrid nanoparticles; catalase-mimicking activity chemo/photothermal therapy; photoacoustic imaging”

Fluorescent PLGA-FKR648 used to track nanoparticles ability to cross the blood-brain-barrier as part of development of HIV treatment

Wednesday, February 7, 2018, 5:34 PM ET

Human immunovirus (HIV) is a wide-spread and incurably lethal disease. The Blood-Brain-Barrier (BBB) separates the brain tissue from the bloodstream and is intended to keep the brain safe from potentially toxic molecules within the bloodstream. One of the more insidious aspects of HIV is the capacity of the virus to ‘hide’ within the brain tissue where most anti-viral medications cannot reach it due to the BBB. This makes treating HIV particularly difficult as the virus can re-infest a patient from surviving copies in the brain tissue, even if the majority of the viral replicates have been destroyed. Recently, researchers at Universidade do Porto (Portugal) and University of Helsinki (Finland) used fluorescent PLGA-FKR648 (PolyVivo AV015) from PolySciTech (www.polyscitech.com) as part of development of BBB crossing nanoparticles to attack HIV virus which hides in the brain. This fluorescently-tagged PLGA was used to develop nanoparticles which could be tracked by microscopy to observe their uptake across the barrier. By visualizing these particles, the researchers were able to validate the success of their particles in crossing the BBB. This research holds promise for improved therapeutic options for HIV. Read more: Martins, Cláudia, Francisca Araújo, Maria João Gomes, Carlos Fernandes, Rute Nunes, Wei Li, Hélder A. Santos, Fernanda Borges, and Bruno Sarmento. "Using microfluidic platforms to develop CNS-targeted polymeric nanoparticles for HIV therapy." European Journal of Pharmaceutics and Biopharmaceutics (2018). https://www.sciencedirect.com/science/article/pii/S0939641117314820

“Abstract: The human immunodeficiency virus (HIV) uses the brain as reservoir, which turns it as a promising target to fight this pathology. Nanoparticles (NPs) of poly(lactic-co-glycolic) acid (PLGA) are potential carriers of anti-HIV drugs to the brain, since most of these antiretrovirals, as efavirenz (EFV), cannot surpass the blood–brain barrier (BBB). Forasmuch as the conventional production methods lack precise control over the final properties of particles, microfluidics emerged as a prospective alternative. This study aimed at developing EFV-loaded PLGA NPs through a conventional and microfluidic method, targeted to the BBB, in order to treat HIV neuropathology. Compared to the conventional method, NPs produced through microfluidics presented reduced size (73 nm versus 133 nm), comparable polydispersity (around 0.090), less negative zeta-potential (−14.1 mV versus −28.0 mV), higher EFV association efficiency (80.7% versus 32.7%) and higher drug loading (10.8% versus 3.2%). The microfluidics-produced NPs also demonstrated a sustained in vitro EFV release (50% released within the first 24 h). NPs functionalization with a transferrin receptor-binding peptide, envisaging BBB targeting, proved to be effective concerning nuclear magnetic resonance analysis (δ = −0.008 ppm; δ = −0.017 ppm). NPs demonstrated to be safe to BBB endothelial and neuron cells (metabolic activity above 70%), as well as non-hemolytic (1–2% of hemolysis, no morphological alterations on erythrocytes). Finally, functionalized nanosystems were able to interact more efficiently with BBB cells, and permeability of EFV associated with NPs through a BBB in vitro model was around 1.3-fold higher than the free drug. Keywords: Nanoparticles; Human immunodeficiency virus; Microfluidic production; Targeting; Blood-brain barrier”

PLGA-PEG-PLGA thermogel from PolySciTech used in development of highly-controlled microwave ablation technique

Monday, January 29, 2018, 2:38 PM ET

Amongst cancer treatments, ablation (the application of heat, cold, or chemicals in a minimally invasive manner directly to the tumor) has gained attention as a method to treat cancer without the systemic damage of chemotherapy or the invasive injuries from standard surgery. One of these techniques, microwave thermal ablation, works by using microwave energy to locally heat the tumor which kills the cancer while minimally affecting surrounding tissues. Recently, Researchers at Brown University/Rhode Island Hospital utilized PolyVivo (AK088) from PolySciTech (www.polyscitech.com) to develop a cesium-salt loaded thermogel which acted to increase the local heating in the vicinity of the tumor improving the effectiveness of thermal ablation. They tested these in an animal model and found the method to be highly effective with minimal side effects. This research holds promise to improve therapeutic options for tumor treatment with minimal side effects. Read more: Park, William Keun Chan, Aaron Wilhelm Palmer Maxwell, Victoria Elizabeth Frank, Michael Patrick Primmer, Jarod Brian Paul, Scott Andrew Collins, Kara Anne Lombardo et al. "The in vivo performance of a novel thermal accelerant agent used for augmentation of microwave energy delivery within biologic tissues during image-guided thermal ablation: a porcine study." International Journal of Hyperthermia 34, no. 1 (2018): 11-18. http://www.tandfonline.com/doi/abs/10.1080/02656736.2017.1317367

“Abstract: Objectives: To investigate the effects of a novel caesium-based thermal accelerant (TA) agent on ablation zone volumes following in vivo microwave ablation of porcine liver and skeletal muscle, and to correlate the effects of TA with target organ perfusion. Materials and methods: This prospective study was performed following institutional animal care and use committee approval. Microwave ablation was performed in liver and resting skeletal muscle in eight Sus scrofa domesticus swine following administration of TA at concentrations of 0 mg/mL (control), 100 mg/mL and 250 mg/mL. Treated tissues were explanted and stained with triphenyltetrazolium chloride (TTC) for quantification of ablation zone volumes, which were compared between TA and control conditions. Hematoxylin and eosin (H&E) staining was also performed for histologic analysis. General mixed modelling with a log-normal distribution was used for all quantitative comparisons (p = 0.05). Results: A total of 28 ablations were performed in the liver and 18 in the skeletal muscle. The use of TA significantly increased ablation zone volumes in a dose-dependent manner in both the porcine muscle and liver (p < 0.01). Both the absolute mean ablation zone volume and percentage increase in ablation zone volume were greater in the resting skeletal muscle than in the liver. In one swine, a qualitative mitigation of heat sink effects was observed by TTC and H&E staining. Non-lethal polymorphic ventricular tachycardia was identified in one swine, treated with intravenous amiodarone. Conclusions: The use of a novel TA agent significantly increased mean ablation zone volumes following microwave ablation using a porcine model. The relationship between TA administration and ablation size was dose-dependent and inversely proportional to the degree of target organ perfusion, and a qualitative reduction in heat-sink effects was observed. Keywords: Image-guided thermal ablation, thermal accelerant, augmentation of microwave energy, complete ablation, the heat sink effect”

PLGA-PEG-Mal and PLGA-PEG-methyl from PolySciTech used in development of oral exanatide-nanoparticle based diabetes treatment

Monday, January 22, 2018, 9:28 AM ET

Medicinal technology developments have several goals, depending on the application. In some cases, the goal is to develop a completely new therapy which did not exist before. In other cases, it is to take an existing therapy and reformulate it to improve either efficacy or convenience. Oral formulations are well known to be more convenient for both patient and practitioner as, unlike parental injections, they can be easily self-administered by a patient, are not painful, and do not require handling/safe-disposal of blood-exposed syringes which could potential spread bloodborne pathogens. Diabetes, notably, requires a great deal of injection-based therapy as part of its treatment. One type of this therapy is Exanatide, a glucagen-like peptide 1 receptor which acts to treat type 2 diabetes. Currently Exanatide is only available as an injectable formulation (Bydureon) as oral uptake is very poor. Recently, researchers at Binzhou Medical University, Yantai University, Luye Pharmaceutical Co, and Peking University (China) use PLGA-PEG-Mal (PolyVivo AI020) and mPEG-PLGA (AK037, AK102) from PolySciTech (www.polyscitech.com) to develop Fc decorated nanoparticles capable of crossing the intestinal mucosa for more effective delivery. This research holds promise to provide for a more convenient and effective therapy for diabetes. Read more: Shi, Yanan, Xinfeng Sun, Liping Zhang, Kaoxiang Sun, Keke Li, Youxin Li, and Qiang Zhang. "Fc-modified exenatide-loaded nanoparticles for oral delivery to improve hypoglycemic effects in mice." Scientific Reports 8, no. 1 (2018): 726. https://www.nature.com/articles/s41598-018-19170-y

“Abstract: To improve the oral efficiency of exenatide, we prepared polyethylene glycol-poly(lactic-co-glycolic acid) (PEG-PLGA) NPs modified with Fc (NPs-Fc) for exenatide oral delivery. Exenatide was encapsulated into the NPs by the w/o/w emulsion-solvent evaporation method. The particle size of the NPs-Fc was approximately 30 nm larger than that of the unmodified NPs with polydispersity indices in a narrow range (PDIs; PDI < 0.3) as detected by DLS, and the highest encapsulation efficiency of exenatide in the NPs was greater than 80%. Fc-conjugated NPs permeated Caco-2 cells faster and to a greater extent compared to unmodified NPs, as verified by CLSM and flow cytometry. Hypoglycemic effect studies demonstrated that oral administration of exenatide-loaded PEG-PLGA NPs modified by an Fc group extended the hypoglycemic effects compared with s.c. injection of the exenatide solution. Fluorescence-labeled NPs were used to investigate the effects of Fc targeting, and the results demonstrated that the NPs-Fc stayed in the gastrointestinal tract for a longer time in comparison with the unmodified NPs, as shown by the whole-body fluorescence images and fluorescence images of the dissected organs detected by in vivo imaging in live mice. Therefore, Fc-targeted nano-delivery systems show great promise for oral peptide/protein drug delivery.”

Mal-PEG-PLGA and mPEG-PLGA from PolySciTech used in development of nanoparticle-based Parkinson’s treatment

Wednesday, January 17, 2018, 9:09 PM ET

Parkinson’s disease is a wide-spread neurodegenerative disorder with over 200,000 USA cases per year. The primary symptoms are loss of control over muscle movements which get progressively worse with time. This disease is caused by damage to dopaminergic neurons which leads to a lack of dopamine in the brain. Although incurable, there are drugs that can delay the progression of Parkinson’s. Because the drug action must occur within the brain, any medicine applied must cross the blood-brain-barrier, a screen that prevents most medicines from reaching the brain. Recently, researchers at Yantai University and Shandong Luye Pharmaceutics utilized mal-PEG-PLGA (Polyvivo AI109) and mPEG-PLGA (PolyVivo AK104) from PolySciTech (www.polyscitech.com) to generate lactoferin-decorated nanoparticles for rotigotine delivery across the blood-brain-barrier as a potential treatment for Parkinson’s disease. This research holds promise to halt the progress of this lethal disease. Read more: Yan X, Xu L, Bi C, Duan D, Chu L, Yu X, Wu Z, Wang A, Sun K “Lactoferrin-modified rotigotine nanoparticles for enhanced nose-to-brain delivery: LESA-MS/MS-based drug biodistribution, pharmacodynamics, and neuroprotective effects” International Journal of Nanomedicine, 9 January 2018 Volume 2018:13 Pages 273—281 https://www.dovepress.com/lactoferrin-modified-rotigotine-nanoparticles-for-enhanced-nose-to-bra-peer-reviewed-fulltext-article-IJN

“Introduction: Efficient delivery of rotigotine into the brain is crucial for obtaining maximum therapeutic efficacy for Parkinson’s disease (PD). Therefore, in the present study, we prepared lactoferrin-modified rotigotine nanoparticles (Lf-R-NPs) and studied their biodistribution, pharmacodynamics, and neuroprotective effects following nose-to-brain delivery in the rat 6-hydroxydopamine model of PD. Materials and methods: The biodistribution of rotigotine nanoparticles (R-NPs) and Lf-R-NPs after intranasal administration was assessed by liquid extraction surface analysis coupled with tandem mass spectrometry. Contralateral rotations were quantified to evaluate pharmacodynamics. Tyrosine hydroxylase and dopamine transporter immunohistochemistry were performed to compare the neuroprotective effects of levodopa, R-NPs, and Lf-R-NPs. Results: Liquid extraction surface analysis coupled with tandem mass spectrometry analysis, used to examine rotigotine biodistribution, showed that Lf-R-NPs more efficiently supplied rotigotine to the brain (with a greater sustained amount of the drug delivered to this organ, and with more effective targeting to the striatum) than R-NPs. The pharmacodynamic study revealed a significant difference (P<0 .05="" 6-hydroxydopamine-induced="" alleviated="" and="" between="" biodistribution="" brain="" conclusion:="" contralateral="" deliver="" disease="" dopaminergic="" drug="" effects="" efficacy.="" efficiently="" enhancing="" findings="" for="" furthermore="" have="" in="" keywords:="" lactoferrin-modified="" lf-r-nps="" might="" model="" more="" nanoparticles="" neurodegeneration="" neuroprotective="" nigrostriatal="" nose="" o:p="" of="" our="" parkinson="" pd.="" pharmacodynamics="" potential="" r-nps.="" rat="" rats="" rotations="" rotigotine="" s="" show="" significantly="" that="" the="" therapeutic="" thereby="" therefore="" those="" to="" treated="" treatment="" with="">

PLGA-PEG-Mal from PolySciTech used in development of immunosuppressant releasing tissue scaffold

Monday, January 1, 2018, 9:28 PM ET

One of the major challenges in stem-cell and tissue engineering is rejection of the new cells by the body through the immune system. Since systemic delivery of immunosuppressant medicines has severe side-effects, a better solution is localized delivery of immunosuppressants to prevent the cells in the scaffold from being attacked by immune cells. Recently, researchers from Fudan University, Tianjin Medical University (China), and Ewha Women’s University (Korea) used PLGA-PEG-Mal (PolyVivo AI136) from PolySciTech (www.polyscitech.com) to create tacrolimus loaded PLGA-PEG- RADA16 self-attractive nanoparticles. These were loaded into stem-cell hydrogels and remained within the hydrogel by electrostatic attraction. This resulted in a consistent and controlled release of immunosuppressant from the scaffold to prevent immune response against the loaded stem cells. This research holds promise to improve results for a wide array of tissue engineering applications. Read more: Li, Ruixiang, Jianming Liang, Yuwei He, Jing Qin, Huining He, Seungjin Lee, Zhiqing Pang, and Jianxin Wang. "Sustained Release of Immunosuppressant by Nanoparticle-anchoring Hydrogel Scaffold Improved the Survival of Transplanted Stem Cells and Tissue Regeneration." Theranostics 2018; 8(4): 878-893. doi: 10.7150/thno.22072 http://www.thno.org/v08p0878.pdf

“The outcome of scaffold-based stem cell transplantation remains unsatisfied due to the poor survival of transplanted cells. One of the major hurdles associated with the stem cell survival is the immune rejection, which can be effectively reduced by the use of immunosuppressant. However, ideal localized and sustained release of immunosuppressant is difficult to be realized, because it is arduous to hold the drug delivery system within scaffold for a long period of time. In the present study, the sustained release of immunosuppressant for the purpose of improving the survival of stem cells was successfully realized by a nanoparticle-anchoring hydrogel scaffold we developed. Methods: Poly (lactic-co-glycolic acid) (PLGA) nanoparticles were modified with RADA16 (RNPs), a self-assembling peptide, and then anchored to a RADA16 hydrogel (RNPs + Gel). The immobilization of RNPs in hydrogel was measured in vitro and in vivo, including the Brownian motion and cumulative leakage of RNPs and the in vivo retention of injected RNPs with hydrogel. Tacrolimus, as a typical immunosuppressant, was encapsulated in RNPs (T-RNPs) that were anchored to the hydrogel and its release behavior were studied. Endothelial progenitor cells (EPCs), as model stem cells, were cultured in the T-RNPs-anchoring hydrogel to test the immune-suppressing effect. The cytotoxicity of the scaffold against EPCs was also measured compared with free tacrolimus-loaded hydrogel. The therapeutic efficacy of the scaffold laden with EPCs on the hind limb ischemia was further evaluated in mice. Results: The Brownian motion and cumulative leakage of RNPs were significantly decreased compared with the un-modified nanoparticles (NPs). The in vivo retention of injected RNPs with hydrogel was obviously longer than that of NPs with hydrogel. The release of tacrolimus from T-RNPs + Gel could be sustained for 28 days. Compared with free tacrolimus-loaded hydrogel, the immune responses were significantly reduced and the survival of EPCs was greatly improved both in vitro and in vivo. The results of histological evaluation, including accumulation of immune cells and deposition of anti-graft antibodies, further revealed significantly lessened immune rejection in T-RNPs-anchoring hydrogel group compared with other groups. In pharmacodynamics study, the scaffold laden with EPCs was applied to treat hind limb ischemia in mice and significantly promoted the blood perfusion (~91 % versus ~36 % in control group). Conclusion: The nanoparticle-anchoring hydrogel scaffold is promising for localized immunosuppressant release, thereby can enhance the survival of transplanted cells and finally lead to successful tissue regeneration. Key words: stem cell; immune suppression; tacrolimus; nanoparticles; endothelial progenitor cells; RADA16 hydrogel.”

Searchable publication listings by product and application available on Akina website

Friday, December 22, 2017, 3:42 PM ET

The number of peer-reviewed journal publications using PST products per year has been steadily increasing over the past several years. This has led to a berth of valuable data regarding the polymer applications and uses. Since this is useful technical data for these products, as much as possible, we try to keep our website up to date with all publications using our products to provide our customers with this valuable resource. If you are interested in PST products for your research and want to get some ideas about how they have been used by others, make sure to visit https://akinainc.com/polyscitech/products/polyvivo/referenced_by.phpfor a full listing of publications. We also have metadata uploaded with keywords and abstracts, so keyword searching can give more details regarding specific applications. Alternatively, if you have used PST materials in a publication and you don’t see it listed, contact jg@akinainc.com with the citation to get it added.

As a side note, this is the last blog posting before Akina closes for 2017. Please note: Akina, Inc. will be closed December 25th through January 2nd for the Christmas and New Year's holidays. Orders placed during this time will be processed when we re-open on Wednesday, January 3rd. Happy Holidays to all.

mPEG-PLA from PolySciTech used in development of nanoparticle treatment to protect brain tissue from inflammation damage

Thursday, December 21, 2017, 4:49 PM ET

One of the major contributing factors to morbidity and death from brain cancer and other neurodegenerative disorders is the inflammation brought on within the brain tissue itself. This leads to swelling, oxidation, and potentially death. Typically treating any ailment that affects the brain is difficult as relatively few medicinal compounds cross from the blood stream into the brain tissue (the blood-brain-barrier). Nanotechnology can be used to improve this however. Recently, researchers at Kent State University and Northeast Ohio Medical University used mPEG-P(DL)La (PolyVivo AK021) from PolySciTech (www.polyscitech.com) to generate a delivery system for simvastatin to protect against neuroinflammation. This research holds promise to reduce damage caused by brain-tumors as well as other diseases implicated with inflammation of neural tissue. Read more: Manickavasagam, Dharani, Kimberly Novak, and Moses O. Oyewumi. "Therapeutic Delivery of Simvastatin Loaded in PLA-PEG Polymersomes Resulted in Amplification of Anti-inflammatory Effects in Activated Microglia." The AAPS Journal 20, no. 1 (2018): 18. https://link.springer.com/article/10.1208/s12248-017-0176-3

“Abstract: Simvastatin (Sim), a lipid-lowering drug has been studied in chronic neuroinflammation associated with degenerative brain disorders due to its potential protective properties against inflammatory reaction, oxidative damage, neuronal dysfunction, and death. Meanwhile, potential application of Sim in neuroinflammation will require a suitable delivery system that can overcome notable challenges pertaining to poor blood–brain barrier (BBB) permeability and side/off-target effects. Herein, we engineered and characterized nano-sized polymersomes loaded with Sim (Sim-Ps) using PEG-PdLLA (methoxy polyethylene glycol-poly(d,l) lactic acid) diblock co-polymers. Studies in BV2 microglia indicated that Sim-Ps was superior to Sim alone in suppressing nitric oxide (NO) and proinflammatory cytokines (interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) secretion against LPS activation. The effectiveness of Sim-Ps as compared with Sim alone, in attenuating NO and cytokine production by activated BV2 cells can be attributed to (a) colloidal stability of the delivery platform, (b) protracted release of biologically active Sim, and (c) particulate internalization coupled with enhanced Sim exposure to BV2 cells. Intranasal delivery in BALB/c mice demonstrated enhanced brain distribution with increasing time after administration. Overall data demonstrated suitability of PEG-PdLLA polymersomes in Sim delivery for potential application in treating neuroinflammation. Key Words: inflammation, microglia, neuroprotection, polymersomes, simvastatin”

mPEG-PLA from PolySciTech investigated for use as an ultrasound contrast-agent

Thursday, December 21, 2017, 4:48 PM ET

Ultrasound imaging is widely used as a diagnostic tool in medicine, but suffers from the drawback of relatively poor contrast. For this reason, this technique is often used after injection of a specific contrast agent, such as microbubbles or liposomes containing mannitol, to provide for improved imaging of features within the tissue. Recently, researchers from The George Washington University and North Dakota State University utilized mPEG-PLLA (Polyvivo AK004) from PolySciTech (www.polyscitech.com) to generate acoustic polymersomes as a contrast agent and investigated their acoustic properties. This research holds promise for improving the diagnostic capabilities of ultrasound. Read more: Xia, Lang, Fataneh Karandish, Krishna Nandan Kumar, James Froberg, Prajakta Kulkarni, Kara N. Gange, Yongki Choi, Sanku Mallik, and Kausik Sarkar. "Acoustic Characterization of Echogenic Polymersomes Prepared From Amphiphilic Block Copolymers." Ultrasound in medicine & biology (2017). https://www.sciencedirect.com/science/article/pii/S0301562917324092

“Abstract: Polymersomes are a class of artificial vesicles prepared from amphiphilic polymers. Like lipid vesicles (liposomes), they too can encapsulate hydrophilic and hydrophobic drug molecules in the aqueous core and the hydrophobic bilayer respectively, but are more stable than liposomes. Although echogenic liposomes have been widely investigated for simultaneous ultrasound imaging and controlled drug delivery, the potential of the polymersomes remains unexplored. We prepared two different echogenic polymersomes from the amphiphilic copolymers polyethylene glycol–poly-DL-lactic acid (PEG-PLA) and polyethylene glycol–poly-L-lactic acid (PEG-PLLA), incorporating multiple freeze-dry cycles in the synthesis protocol to ensure their echogenicity. We investigated acoustic behavior with potential applications in biomedical imaging. We characterized the polymeric vesicles acoustically with three different excitation frequencies of 2.25, 5 and 10 MHz at 500 kPa. The polymersomes exhibited strong echogenicity at all three excitation frequencies (about 50- and 25-dB enhancements in fundamental and subharmonic, respectively, at 5-MHz excitation from 20 µg/mL polymers in solution). Unlike echogenic liposomes, they emitted strong subharmonic responses. The scattering results indicated their potential as contrast agents, which was also confirmed by clinical ultrasound imaging. Key Words: Ultrasound imaging; Contrast agent; Microbubble; Polymersomes; Echogenic; Drug delivery”

mPEG-PLGA from PolySciTech used in development of microparticle-based delivery system for regulatory T-cell induction factors as an anti-inflammatory therapy

Tuesday, December 19, 2017, 8:59 AM ET

Several diseases and conditions are associated with an excessive immune response which leads to inflammation that can damage tissue. There are medicines available which can reduce the immune response (e.g. anti-histamines, steroidal anti-inflammatories) however, these all have side-effects due to their relatively non-specific nature in globally preventing immune response. The immune system itself has a built-in regulatory mechanism which acts through regulatory T-cells that act to reduce immune response and improve the recognition of antigens as ‘self.’ A more effective and therapeutic strategy is to provide factors which promote the formation and recruitment of regulatory t-cells to a site of inflammation. Recently, researchers at The University of Pittsburgh used mPEG-PLGA (PolyVivo AK037) from PolySciTech (www.polyscitech.com) to create a microparticle designed to release pro-regulatory-t-cell factors into the eye as a means to reduce localized inflammation by promoting the body’s own feedback system to control the immune response. This research holds promise not only to treat ocular diseases, but to be applied to other disease in which excessive immune response is implicated. Read more: Ratay, Michelle L., Stephen C. Balmert, Abhinav P. Acharya, Ashlee C. Greene, Thiagarajan Meyyappan, and Steven R. Little. "TRI Microspheres prevent key signs of dry eye disease in a murine, inflammatory model." Scientific Reports 7, no. 1 (2017): 17527. https://www.nature.com/articles/s41598-017-17869-y

“Abstract: Dry eye disease (DED) is a highly prevalent, ocular disorder characterized by an abnormal tear film and ocular surface. Recent experimental data has suggested that the underlying pathology of DED involves inflammation of the lacrimal functional unit (LFU), comprising the cornea, conjunctiva, lacrimal gland and interconnecting innervation. This inflammation of the LFU ultimately results in tissue deterioration and the symptoms of DED. Moreover, an increase of pathogenic lymphocyte infiltration and the secretion of pro-inflammatory cytokines are involved in the propagation of DED-associated inflammation. Studies have demonstrated that the adoptive transfer of regulatory T cells (Tregs) can mediate the inflammation caused by pathogenic lymphocytes. Thus, as an approach to treating the inflammation associated with DED, we hypothesized that it was possible to enrich the body’s own endogenous Tregs by locally delivering a specific combination of Treg inducing factors through degradable polymer microspheres (TRI microspheres; TGF-β1, Rapamycin (Rapa), and IL-2). This local controlled release system is capable of shifting the balance of Treg/T effectors and, in turn, preventing key signs of dry eye disease such as aqueous tear secretion, conjunctival goblet cells, epithelial corneal integrity, and reduce the pro-inflammatory cytokine milieu in the tissue.”

PLA-Fluorescein from PolySciTech used in PhD thesis work on development of theranostic nanoparticles for treatment of heart-disease

Monday, December 18, 2017, 2:14 PM ET

A critical yet often overlooked factor in atherosclerosis (heart-disease) is inflammation, as swelling contributes to the constriction of the blood vessels and damage to the tissue. This also presents a potential therapeutic target as preventing inflammation can assist with reducing the incidence of morbidity and mortality with this disease. Recently, researchers at Massachusetts Institute of Technology used P(DL)La and P(DL)La-Fluorescein (PolyVivo AV016) from PolySciTech (www.polyscitech.com) to develop nanoparticles to deliver simvastatin to affected tissue. The use of fluorescein conjugated PLA allowed for easy tracking of the nanoparticles by visual techniques. This research holds promise to treat inflammatory diseases. Read more: Chung, Bomy Lee. "Theranostic nanoparticles for the management of inflammatory diseases and conditions." PhD diss., Massachusetts Institute of Technology, 2017. https://dspace.mit.edu/handle/1721.1/112504

“Abstract: Atherosclerosis, the gradual buildup of plaques within arteries, is the main cause of cardiovascular diseases (CVDs). The World Health Organization reports that CVDs are the number one cause of death in the world. In the United States alone, around 85 million people suffer from CVDs; this is associated with a cost of over $316 billion per year and responsible for about a third of all deaths in the US. Recent findings have shown that inflammation plays a pivotal role in atherosclerosis. Although statins have traditionally been prescribed for their lipid-lowering benefits, studies have indicated that they can have other effects as well (so-called "pleiotropic effects"), including anti-inflammatory, anti-oxidant, and anti-thrombotic benefits. This thesis presents a novel theranostic (therapeutic + diagnostic) nanoparticle platform for the treatment and diagnosis of atherosclerosis. Given the anti-inflammatory effects of statins when cells are directly treated, the aim of this nanoparticle platform was to target macrophages within plaques given their central role in plaque development and progression. First, simvastatin-loaded nanoparticles were designed and optimized. The particles consisted of a biodegradable polymer core and a lipid shell. Using bulk nanoprecipitation methods, as well as microfluidic devices, the physical characteristics of the particles could be controlled and fine-tuned to meet the desired specifications: 100 to 200 nm in size, -15 to -20 mV in zeta potential, and 70%+ simvastatin loading efficiency. Imaging agents, such as iron oxide nanocrystals used for magnetic resonance imaging (MRI), were successfully incorporated into the nanoparticles and can offer diagnostic capabilities to the nanoparticles. Next, various nanoparticle formulations were shown to be therapeutically effective in cell and mice models of atherosclerosis. For instance, in vitro treatment of macrophages led to decreases in the expression of TNF-a and MCP-1 by roughly 20% and 50%, respectively. This pattern has also been observed in murine models, with researchers showing that simvastatin-loaded particles can halt plaque development (and even decrease plaque area) while reducing the expression of pro-inflammatory genes (e.g., of TNF-a, IL- IP) by an order of magnitude. Overall, this thesis presents a new and innovative nanoparticle platform that has the potential for the simultaneous treatment and diagnosis of atherosclerosis. Given their anti-inflammatory benefits, these nanoparticles have the potential to impact the treatment of not only atherosclerosis but also various other inflammatory conditions and diseases as well.”

PLGA from PolySciTech used in developing Bioadhesive hydrogels for tissue-engineering applications

Monday, December 18, 2017, 2:13 PM ET

As a general rule, it is very difficult to have a material which adheres well to biological tissues. Biological tissues are warm, wet, and typically covered with a coating of proteins which tend to reduce adhesion. This makes designing adhesives for them very difficult. For tissue engineering applications it is critical that whatever scaffold or patch is applied, remains well-adhered to the tissue for it to work. The adhesive must also be biocompatible. Interestingly, a solution for bioadhesion has presented itself in nature from barnacles/mussels, which secrete an incredibly adhesive biopolymer to hold onto rocks. Recently, researchers at University of Texas at Arlington, used PLGA (PolyVivo AP154) from PolySciTech (www.polyscitech.com) to create nanoparticles to improve the bioadhesion of barnacle/mussel-inspired alginate-dopa hydrogels. This research holds promise for improved tissue engineering patches and scaffolds to treat wounds and defects. Read more: Pandey, Nikhil, Amirhossein Hakamivala, Cancan Xu, Prashant Hariharan, Boris Radionov, Zhong Huang, Jun Liao et al. "Biodegradable Nanoparticles Enhanced Adhesiveness of MusselLike Hydrogels at Tissue Interface." Advanced healthcare materials (2017). http://onlinelibrary.wiley.com/doi/10.1002/adhm.201701069/full

“Abstract: Popular bioadhesives, such as fibrin, cyanoacrylate, and albumin–glutaraldehyde based materials, have been applied for clinical applications in wound healing, drug delivery, and bone and soft tissue engineering; however, their performances are limited by weak adhesion strength and rapid degradation. In this study a mussel-inspired, nanocomposite-based, biodegradable tissue adhesive is developed by blending poly(lactic-co-glycolic acid) (PLGA) or N-hydroxysuccinimide modified PLGA nanoparticles (PLGA-NHS) with mussel-inspired alginate–dopamine polymer (Alg-Dopa). Adhesive strength measurement of the nanocomposites on porcine skin–muscle constructs reveals that the incorporation of nanoparticles in Alg-Dopa significantly enhances the tissue adhesive strength compared to the mussel-inspired adhesive alone. The nanocomposite formed by PLGA-NHS nanoparticles shows higher lap shear strength of 33 ± 3 kPa, compared to that of Alg-Dopa hydrogel alone (14 ± 2 kPa). In addition, these nanocomposites are degradable and cytocompatible in vitro, and elicit in vivo minimal inflammatory responses in a rat model, suggesting clinical potential of these nanocomposites as bioadhesives.”

mPEG-PLGA from PolySciTech used in development of combination chemotherapy nanoparticles for treatment of lung cancer

Monday, December 18, 2017, 2:10 PM ET

Lung cancer is a prevalent and deadly disease contributing to about 222,500 new cases and 155,870 deaths per year in America alone. Lung cancer propagates itself through cancer stem-cells, cells within cancer which can differentiate into multiple cell types. Treating the cancer requires both eliminating the mature cancer cells and the stem-cells, so that the cancer cannot grow back. Recently, researchers at Xiangyang Central Hospital and Second Military Medical University (China) used mPEG-PLGA (PolyVivo AK101) from PolySciTech (www.polyscitech.com) to generate salinomycin and gefitinib loaded nanoparticles for lung cancer treatment. This research holds promise to develop more effective treatment strategies for this disease by eliminating both cancer cells and cancer stem cells. Read more: Zhang, Yu, Qi Zhang, Jing Sun, Huijie Liu, and Qingfeng Li. "The combination therapy of salinomycin and gefitinib using poly (D, L-lactic-co-glycolic acid)-poly (ethylene glycol) nanoparticles for targeting both lung cancer stem cells and cancer cells." OncoTargets and therapy 10 (2017): 5653. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5709995/

“Abstract: Purpose: Lung cancer (LC) is the leading cause of cancer death worldwide. Evidences suggest that both LC cancer stem cells (CSCs) and cancer cells are supposed to be eliminated to achieve superior treatment effect against LC. Salinomycin could eradiate CSCs in various types of cancers, and gefitinib is a first-line therapy in LC. The purpose of the present study was to develop salinomycin-loaded nanoparticles (salinomycin-NPs) combined with gefitinib-loaded nanoparticles (gefitinib-NPs) to eradicate both LC CSCs and cancer cells. Methods: Salinomycin and gefitinib were encapsulated separately by poly(d,l-lactic-co-glycolic acid)-poly(ethylene glycol) nanoparticles by the emulsion/solvent evaporation approach. The anti-LC activity of salinomycin-NPs and gefitinib-NPs was investigated. Results: Salinomycin-NPs and gefitinib-NPs are of ~140 nm in size, high drug encapsulation efficacy and sustained release of drugs. CD133+ LC CSCs showed the characteristics of CSCs, including significantly enhanced stem cell gene expression, tumorsphere formation ability, and tumorigenicity in mice. Both salinomycin and salinomycin-NPs are capable of selectively inhibiting LC CSCs, as reflected by their enhanced cytotoxic effects toward CD133+ LC CSCs and ability to reduce tumorsphere formation in LC cell lines, whereas gefitinib and gefitinib-NPs could significantly inhibit LC cells. Salinomycin-NPs and salinomycin could reduce the population of LC CSCs in the tumors in vivo. It is noteworthy that salinomycin-NPs combined with gefitinib-NPs inhibited the growth of tumors more efficiently compared with salinomycin combined with gefitinib or single salinomycin-NPs or gefitinib-NPs. Conclusion: Salinomycin-NPs combined with gefitinib-NPs represent a potential approach for LC by inhibiting both LC CSCs and cancer cells. Keywords: cancer stem cells, lung cancer, nanoparticles, salinomycin, gefitinib”

PLGA and PLGA-PEG-Mal from PolySciTech used in development of cancer immunotherapy

Friday, December 15, 2017, 10:09 PM ET

One of the more insidious facets of cancer is that, for a variety of biochemical reasons, most cancers do not elicit an immune response from the body. The human body’s immune system is well adept at thwarting foreign cells and pathogens and is very capable of destroying many cancer cells once activated. For this reason, there has been a great deal of research in ‘immunotherapy’ which is effectively a process of vaccinating the human body against cancer so that it recognizes and destroys cancer cells as though they were pathogens. This provides for a much more selective therapy overall as compared to conventional cytotoxic chemotherapies. Recently, researchers at Dana Faber, Harvard Medical School, MIT, Howard Hughes Medical Institute, and Koch Institute for Integrative Cancer Research utilized Mal-PEG-PLGA (Cat# AI053) and PLGA (Cat # AP041) from PolySciTech (www.polyscitech.com) to generate nanoparticles with reactive exteriors. These nanoparticles were conjugated to targeting ligands via Michael’s reaction between the maleimide units and thiol-bearing antibody fragments. The formed nanoparticles were found to target immune cells and deliver immunotherapy agents to them. This research holds promise for enhanced cancer therapy. Read more: Cartwright, A.N., Hartl, C.A., Park, C.G., Schmid, D., Irvine, D.J., Freeman, G.J., Maiarana, J., Wucherpfennig, K.W., Goldberg, M.S., Subedi, N. and Puerto, R.B., 2017. T cell-targeting nanoparticles focus delivery of immunotherapy to improve antitumor immunity. Nature communications, 8, p.1747. https://www.nature.com/articles/s41467-017-01830-8

“Abstract: Targeted delivery of compounds to particular cell subsets can enhance therapeutic index by concentrating their action on the cells of interest. Because attempts to target tumors directly have yielded limited benefit, we instead target endogenous immune cell subsets in the circulation that can migrate actively into tumors. We describe antibody-targeted nanoparticles that bind to CD8+ T cells in the blood, lymphoid tissues, and tumors of mice. PD-1+ T cells are successfully targeted in the circulation and tumor. The delivery of an inhibitor of TGFβ signaling to PD-1-expressing cells extends the survival of tumor-bearing mice, whereas free drugs have no effect at such doses. This modular platform also enables PD-1-targeted delivery of a TLR7/8 agonist to the tumor microenvironment, increasing the proportion of tumor-infiltrating CD8+ T cells and sensitizing tumors to subsequent anti-PD-1. Targeted delivery of immunotherapy to defined subsets of endogenous leukocytes may be superior to administration of free drugs.”

These posts are syndicated from John Garner's blog at http://jgakinainc.blogspot.com/ where you can post a question or comment.


Social Media

Facebook Twitter Google+ LinkedIn Google Blogger Hyperactive polymer ACS network

Help us improve. We welcome your feedback: SIGN IN or be ANONYMOUS.

logoHome Page | Copyright 2018 Akina, Incorporated | 3495 Kent Avenue, West Lafayette, Indiana 47906 | (765) 464-0390
Official website of Akina, Inc.