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.


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PLGA-PEG-PLGA thermogel from PolySciTech used in development of bone-tuberculosis therapy

Monday, January 14, 2019, 4:40 PM ET

Although tuberculosis is commonly associated with the lungs, this bacterial infection can also affect other body parts such as the spinal column (Pott’s disease) or long-bones. This form of the disease is both difficult to diagnose (until it is in late stages) and can lead to severe problems, including neurological problems and paralysis. Typically, transfer of medicinal molecules into bone tissue is poor due to weak vascularization and poor blood flow. In this case, achieving a useful concentration of anti-tuberculosis agent in the bones requires very high dosing of the agent throughout the entire body, which can lead to problematic side effects. Recently, researchers at Central South University (China) used PLGA-PEG-PLGA (AK097) from PolySciTech (www.polyscitech.com) to generate Isoniazid loaded hydrogel. Since the gel can be injected directly to site, this could be used to treat bone tuberculosis without requiring a high dose of the drug across the entire body. This research holds promise to improve treatments for this debilitating disease. Read more: Liu, Peng, Binbin Guo, Shengfeng Wang, Jinsong Ding, and Wenhu Zhou. "A Thermo-Responsive and Self-Healing Liposome-in-Hydrogel System as an Antitubercular Drug Carrier for Localized Bone Tuberculosis Therapy." International Journal of Pharmaceutics (2019). https://www.sciencedirect.com/science/article/pii/S0378517319300201

“Abstract: Isoniazid (INH) is a first-line therapy for bone tuberculosis (TB), but its clinic benefits are limited by severe side-effects after long-time administration. While nano-drug delivery systems present as promising strategies for INH delivery, the therapeutic efficacies are usually suboptimal due to ineffective drug accumulation at diseased sites. Local delivery system can achieve high drug concentration at focus sites with minimal systemic exposure, and herein we aimed to employ this strategy to develop a novel liposome-in-hydrogel system for localized treatment of bone TB. To achieve sustainable drug release, a derivative of INH called DINH was loaded because of its hydrophobicity, as well as its better activity and higher biosafety than INH. The hybrid system was demonstrated for thermo-responsive and self-healing properties via phase transition test and rheological studies, which were particularly useful for intra-articular administration. In vivo microdialysis studies revealed that the system can rapidly release drug into synovial fluid to reach effective inhibitory concentrations after localized injection, followed by a steady-state drug release. The optical image studies were performed to study its long-term behavior in vivo, which suggested a sustained drug release profile for several days. This work provides a promising drug delivery system for bone TB therapy. Keywords: Bone tuberculosis Isoniazid Liposomes Thermo-responsive hydrogel Self-healing”

PLGA from PolySciTech used in development of oral exenatide formulation for diabetes treatment

Tuesday, January 8, 2019, 11:52 AM ET

Diabetes is a highly prevalent disease affecting roughly 30.3 million Americans, leading to nearly 79,000 deaths annually, making it the 7th leading cause of death (ADA, 2015 statistics). Exenatide is a GLP-1 (glucagon-like peptide-1) agonist used to treat type-2 diabetes. Exenatide’s poor bioavailability requires it to be administered as an injection. Since diabetes is a chronic disease, it is preferable for therapy to be easy for patients to self-administer such as an oral formulation (tablet or pill). Recently, researchers at Yantai University (China) used PLGA (Polyvivo AP081) from PolySciTech (www.polyscitech.com) to develop a nanoparticle-exenatide formulation to improve uptake across the intestine for better bioavailability. This research holds promise for improved treatment options for diabetes. Read more: Song, Yina, Yanan Shi, Liping Zhang, Haiyan Hu, Chunyan Zhang, Miaomiao Yin, Liuxiang Chu et al. "Synthesis of CSK-DEX-PLGA nanoparticles for oral delivery of exenatide to improve its mucus penetration and intestinal absorption." Molecular Pharmaceutics (2019). https://pubs.acs.org/doi/abs/10.1021/acs.molpharmaceut.8b00809

“Abstract: Oral absorption of exenatide, a drug for type 2 diabetes treatment, can be improved by using nanoparticles (NPs) for its delivery. To improve the mucus penetration and intestinal absorption of exenatide, we designed a block copolymer, CSKSSDYQC-dextran-poly (lactic-co-glycolic acid) (CSK-DEX-PLGA), and used it for preparation of exenatide-loaded NPs. The functionalized exenatide-loaded NPs composed of CSK-DEX-PLGA were able to target intestinal epithelial cells and reduce the mucus-blocking effect of the intestine. Moreover, the CSK modification of DEX-PLGA was found to significantly promote the absorption efficiency of NPs in the small intestine, based on in vitro ligation of intestinal rings and examination of different intestinal absorption sites. Compared with DEX-PLGA-NPs (DPs), the absorption of CSK-DEX-PLGA-NPs (CDPs) was increased in the villi, allowing the drug to act on goblet-like Caco-2 cells through clathrin-, caveolin- and gap-mediated endocytosis. Furthermore, enhanced transport ability of CDPs was observed in a study on Caco-2/HT-29-MTX co-cultured cells. CDPs exhibited a prolonged hypoglycemic response with a relative bioavailability of 9.2% in diabetic rats after oral administration. In conclusion, CDPs can target small intestinal goblet cells and have a beneficial effect on oral administration of macromolecular peptides as a nanometer-sized carrier.”

Just in time for New Years: PLGA-NH2 from PolySciTech used in development of obesity treatment

Wednesday, January 2, 2019, 4:28 PM ET

Around New Year’s, many people begin forming resolutions several of which involve losing weight. There are many causes and factors which contribute to weight gain and obesity. One of which is the disposition of metabolic energy derived from food, whether it is consumed in muscular contractions (exercise), used in biochemical functions (regular homeostasis maintenance), generation of heat or stored as fat. Recently, researchers at Purdue University published a patent describing the use of PLGA-NH2 (Polyyvivo AI010) from PolySciTech (www.polyscitech.com) as part of nanoparticle therapy to encourage fatty cells to convert energy into heat rather than storing it as fat. This research holds promise to help in reduction of obesity and related cardiovascular and other diseases associated with this condition. Read more: Deng, Meng, Chunhui Jiang, Liangju Kuang, and Shihuan Kuang. "Polymer-based therapeutics for inductive browning of fat." U.S. Patent Application 15/771,312, filed November 15, 2018. https://patents.google.com/patent/US20180326080A1/en

“Abstract: This disclosure features the methods and compositions involving development of novel polymer-based therapeutics that induce browning of white adipocytes for the treatment of obesity and its associated metabolic diseases. The therapeutic effects are largely attributed to the promotion of brown and/or beige adipocyte development and function by leveraging adipocyte plasticity and polymer-based drug delivery systems. Both brown and beige adipocytes are densely packed with mitochondria which highly express uncoupling protein-1 (UCP1), a thermogenic protein mediating non-shivering thermogenesis.”

Date and Location Set for 2019 BPCR Conference: August 28th KPTC

Wednesday, December 12, 2018, 3:50 PM ET

Last year saw the first annual Biotech, Pharma, Cancer, Research (BPCR) conference sponsored by Akina, Inc. come to beautiful fruition. This scientific networking conference held in Purdue Research Park provides for an opportunity for scientists across academia, corporate, and other institutions to meet and discuss their ideas, needs, and collaboration opportunities. The date and location for 2019 have been set as August 28th in Kurz Purdue Technology Center (KPTC). Keep an eye out for more updates as well as opportunities to present and promote here: http://bpcrconference.com/

Amine-PEG-PLGA from PolySciTech used in development of antibiotic formulation against food-borne illness

Tuesday, December 11, 2018, 10:59 AM ET

Although often overlooked, the impact of foodborne illness on society is not trivial. The CDC estimates 48 million are afflicted with 128K hospitalizations and roughly 3000 deaths from foodborne illness each year in USA (https://www.cdc.gov/foodborneburden/index.html). Rosin acids (from conifer trees) are a class of compounds which have good efficacy against a wide range of bacteria, but suffer from poor solubility and side-effects that limits their clinical usefulness. Recently, researchers at the Instituo de Investigacao e Inovacao, em Saude (Portugal) and the Institute of Sciences of Food Production, National Research Council (Italy) used amine-PEG-PLGA (AI058) from PolySciTech (www.polyscitech.com) to create rosin-acid bound nanoparticles and assayed these particles for their efficacy against bacteria. This research holds promise to improve therapies against foodborne illness including antibiotic resistant strains. Read more: Santovito, Elisa, José das Neves, Donato Greco, Vito D’Ascanio, Bruno Sarmento, Antonio Francesco Logrieco, and Giuseppina Avantaggiato. "Antimicrobial properties of rosin acids-loaded nanoparticles against antibiotic-sensitive and antibiotic-resistant foodborne pathogens." Artificial Cells, Nanomedicine, and Biotechnology (2018): 1-9. https://www.tandfonline.com/doi/abs/10.1080/21691401.2018.1496924

“Abstract: Rosin acids (RA) from coniferous trees are used in folk medicine for healing various skin infections. Despite the antimicrobial potential of RA, their poor solubility in aqueous media may limit their use. In this work RA-loaded polyethylene glycol-poly(lactic-co-glycolic acid) nanoparticles (RA-NPs) with enhanced antimicrobial properties against foodborne bacterial pathogens were produced. RA-NPs were prepared by solvent displacement technique and characterized for relevant colloidal features by dynamic light scattering, laser Doppler anemometry and transmission electron microscopy. Association of RA to NPs occurred with high yields (86% w/w). RA and RA-NPs (∼130 nm) were strongly active against antibiotic-sensitive Gram + pathogens, i.e. Clostridium perfringens, Listeria monocytogenes and antibiotic-resistant Staphylococcus aureus. However, both failed in inhibiting the growth of Gram – pathogens (Campylobacter jejuni, Campylobacter coli, Escherichia coli and Salmonella enterica). Association to NPs enhanced the antimicrobial activity of RA. MIC, IC50, IC90, and MBC values of RA-NPs were ten-times lower than RA. RA-NPs did not change the intrinsic toxicity potential of RA. This is the first study on the enhancement of the antimicrobial activity of RA when associated to nanocarriers. This approach may be an effective strategy to produce aqueous-based RA solutions with enhanced antimicrobial activity against antibiotic-sensitive and antibiotic-resistant Gram + pathogens. Keywords: Nanoparticles, antimicrobials, rosinic acids, pathogenic bacteria, nanocarriers”

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PLGA from PolySciTech used in development of nanoparticle-bacteria hybrid autonomous drug delivery system for cancer therapy

Monday, December 10, 2018, 4:13 PM ET

Typhimurium VNP20009 is a recently developed non-pathogenic bacterium which has displayed targeting towards cancer cells. Nanoparticles attached to this bacterium follow it along as it readily penetrates into hypoxic tumor regions. Recently, researchers at Virginia Tech University utilized PLGA (AP082) from PolySciTech (www.polyscitech.com) to create bacteria-nanoparticle hybrid carrier system to target tumors. This research holds promise to treat tumors in poorly vascular areas that conventional therapies cannot easily reach. Read more: Suh, SeungBeum, Ami Jo, Mahama A. Traore, Ying Zhan, Sheryl L. Coutermarsh‐Ott, Veronica M. Ringel‐Scaia, Irving C. Allen, Richey M. Davis, and Bahareh Behkam. "Nanoscale Bacteria‐Enabled Autonomous Drug Delivery System (NanoBEADS) Enhances Intratumoral Transport of Nanomedicine." Advanced Science (2018): 1801309. https://onlinelibrary.wiley.com/doi/abs/10.1002/advs.201801309

“Abstract: Cancer drug delivery remains a formidable challenge due to systemic toxicity and inadequate extravascular transport of nanotherapeutics to cells distal from blood vessels. It is hypothesized that, in absence of an external driving force, the Salmonella enterica serovar Typhimurium could be exploited for autonomous targeted delivery of nanotherapeutics to currently unreachable sites. To test the hypothesis, a nanoscale bacteria‐enabled autonomous drug delivery system (NanoBEADS) is developed in which the functional capabilities of the tumor‐targeting S. Typhimurium VNP20009 are interfaced with poly(lactic‐co‐glycolic acid) nanoparticles. The impact of nanoparticle conjugation is evaluated on NanoBEADS' invasion of cancer cells and intratumoral transport in 3D tumor spheroids in vitro, and biodistribution in a mammary tumor model in vivo. It is found that intercellular (between cells) self‐replication and translocation are the dominant mechanisms of bacteria intratumoral penetration and that nanoparticle conjugation does not impede bacteria's intratumoral transport performance. Through the development of new transport metrics, it is demonstrated that NanoBEADS enhance nanoparticle retention and distribution in solid tumors by up to a remarkable 100‐fold without requiring any externally applied driving force or control input. Such autonomous biohybrid systems could unlock a powerful new paradigm in cancer treatment by improving the therapeutic index of chemotherapeutic drugs and minimizing systemic side effects.”

mPEG-PCL from PolySciTech used in development of oral pancreatic cancer therapy

Friday, December 7, 2018, 4:01 PM ET

There are many medicinal compounds which are clinically effective but lack adequate oral bioavailability. Low bioavailability can be overcome through a variety of formulatory approaches. Recently, researchers at Alexandria University used mPEG-PCL (AK105) from PolySciTech (www.polyscitech.com) to develop polymersomes with improved bioavailability. This research holds promise for improved therapy of pancreatic cancer. Read more: Youssef, Shams F., Yosra SR Elnaggar, and Ossama Y. Abdallah. "Elaboration of polymersomes versus conventional liposomes for improving oral bioavailability of the anticancer flutamide." Nanomedicine 00 (2018). https://www.futuremedicine.com/doi/abs/10.2217/nnm-2018-0238

“Aim: Flutamide is an outstanding anticancer drug with poor oral bioavailability. This is the first work to investigate the potential of polymersomes versus conventional liposomes to improve flutamide bioavailability. Materials & methods: Polymersomes were prepared by solvent-switching technique and successfully optimized with excellent nanometric size (143 nm) and ζ-potential (-33.4 mV). Physicochemical characterization, stability in gastrointestinal tract and in vivo oral pharmacokinetics in male Sprague–Dawely rats were performed. Results: A significantly higher stability in simulated intestinal fluid was demonstrated by polymersomes compared with liposomes. Great improvement in flutamide oral bioavailability in polymersomes compared with both liposomes and drug suspension was obtained. Conclusion: Polymersomes are promising nanoplatforms to overcome stability problems of liposomes and to improve flutamide oral bioavailability. Keywords: flutamide liposomes oral bioavailability pharmacokinetics polymersomes prostate cancer”

Polymer 106: Drug Delivery

Thursday, December 6, 2018, 5:08 PM ET

Drug delivery technology and applications including intestinal uptake, targeted nanoparticle therapy, and crossing the blood-brain-barrier explained through a humorous encounter with TSA.

PLGA-FITC and PLGA-NH2 from PolySciTech used in development of quinic-acid decorated nanoparticles for cancer delivery

Tuesday, December 4, 2018, 11:52 AM ET

Due to the toxicity of most chemotherapeutic agents, there is a need to ensure the preferential localization of these compounds into the tumor site for appropriate activity. One compound, quinic acid, has presented promise for use as a targeting ligand against tumor cells. Recently, researchers at Purdue University used PLGA-NH2 (AI017) and PLGA-FITC (AV001) from PolySciTech (www.polyscitech.com) to develop and test nanoparticles for uptake to tumors. This research holds promise for improved therapies against cancer. Read more: Xu, Jun, Steve Seung‐Young Lee, Howon Seo, Liang Pang, Yearin Jun, Ruo‐Yu Zhang, Zhong‐Yin Zhang et al. "Quinic Acid‐Conjugated Nanoparticles Enhance Drug Delivery to Solid Tumors via Interactions with Endothelial Selectins." Small (2018): 1803601. https://onlinelibrary.wiley.com/doi/abs/10.1002/smll.201803601

“Abstract: Current nanoparticle (NP) drug carriers mostly depend on the enhanced permeability and retention (EPR) effect for selective drug delivery to solid tumors. However, in the absence of a persistent EPR effect, the peritumoral endothelium can function as an access barrier to tumors and negatively affect the effectiveness of NPs. In recognition of the peritumoral endothelium as a potential barrier in drug delivery to tumors, poly(lactic‐co‐glycolic acid) (PLGA) NPs are modified with a quinic acid (QA) derivative, synthetic mimic of selectin ligands. QA‐decorated NPs (QA‐NP) interact with human umbilical vein endothelial cells expressing E‐/P‐selectins and induce transient increase in endothelial permeability to translocate across the layer. QA‐NP reach selectin‐upregulated tumors, achieving greater tumor accumulation and paclitaxel (PTX) delivery than polyethylene glycol‐decorated NPs (PEG‐NP). PTX‐loaded QA‐NP show greater anticancer efficacy than Taxol or PTX‐loaded PEG‐NP at the equivalent PTX dose in different animal models and dosing regimens. Repeated dosing of PTX‐loaded QA‐NP for two weeks results in complete tumor remission in 40–60% of MDA‐MB‐231 tumor‐bearing mice, while those receiving control treatments succumb to death. QA‐NP can exploit the interaction with selectin‐expressing peritumoral endothelium and deliver anticancer drugs to tumors to a greater extent than the level currently possible with the EPR effect.”

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Mal-PEG-PLGA and mPEG-PLGA from PolySciTech used in development of nanoparticle pancreatic-cancer therapy

Thursday, November 29, 2018, 10:45 AM ET

Pancreatic ductal adenocarcinoma (PDA) is a difficult to treat and typically fatal form of pancreatic cancer. Part of the difficulty in treatment is the relatively low vascularization in the tumor region for this type of cancer which prevents uptake of medicinal therapies. Use of nanoparticles decorated with a targeting ligand could improve drug delivery to this region. Recently, researchers at Harvard Medical School used mPEG-PLGA (AK102) and mal-PEG-PLGA (AI110) from PolySciTech (www.polyscitech.com) to develop nanoparticles covered with MECA79 targeting antibody and investigated their transport and uptake. This research holds promise for improved therapies against this fatal disease. Read more: Baharak Bahmani, Mayuko Uehara, Farideh Ordikhani, Xiaofei Li, Liwei Jiang, Naima Banouni, Takaharu Ichimura, Vivek Kasinath, Siawosh K. Eskandari, Nasim Annabi, Jonathan S. Bromberg, Leonard D. Shultz, Dale L. Greiner, Reza Abdi “Ectopic high endothelial venules in pancreatic ductal adenocarcinoma: A unique site for targeted delivery” EBioMedicine (2018) Read more: https://www.ebiomedicine.com/article/S2352-3964(18)30534-6/fulltext

“Background: Nanomedicine offers an excellent opportunity to tackle treatment-refractory malignancies by enhancing the delivery of therapeutics to the tumor site. High endothelial venules (HEVs) are found primarily in lymph nodes or formed de novo in peripheral tissues during inflammatory responses. They express peripheral node addressin (PNAd), which is recognized by the monoclonal antibody MECA79. Methods: Here, we demonstrated that HEVs form de novo in human pancreatic ductal adenocarcinoma (PDAC). We engineered MECA79 coated nanoparticles (MECA79-NPs) that recognize these ectopic HEVs in PDAC. Findings: The trafficking of MECA79-NPs following intravenous delivery to human PDAC implanted in a humanized mouse model was more robust than non-conjugated NPs. Treatment with MECA79-Taxol-NPs augmented the delivery of Paclitaxel (Taxol) to the tumor site and significantly reduced the tumor size. This effect was associated with a higher apoptosis rate of PDAC cells and reduced vascularization within the tumor. Interpretation: Targeting the HEVs of PDAC using MECA79-NPs could lay the ground for the localized delivery of a wide variety of drugs including chemotherapeutic agents.”

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mPEG-PLGA and PLGA from PolySciTech used in development of nanoparticle combination therapy for brain-cancer treatment

Monday, November 19, 2018, 11:15 AM ET

Glioblastoma is a form of brain-cancer that is highly aggressive with a 15-16 month median patient survival rate. Use of nanoparticles which may cross the blood-brain-barrier, along with combination therapeutic approaches, may provide further treatment options. Recently, researchers at University of Massachusetts Lowell used mPEG-PLGA (PolyVivo AK037) and PLGA (AP041) from PolySciTech (www.polyscitech.com) to create nanoparticles loaded with a combination of photosensitizers and chemotherapy agents for treatment against this disease. This research holds promise to provide for improved therapeutic options against this fatal disease. Read more: Kydd, Janel, Rahul Jadia, and Prakash Rai. "Co-Administered Polymeric Nano-Antidotes for Improved Photo-Triggered Response in Glioblastoma." Pharmaceutics 10, no. 4 (2018): 226. https://www.mdpi.com/1999-4923/10/4/226/htm

“Abstract: Polymer-based nanoparticles (NPs) are useful vehicles in treating glioblastoma because of their favorable characteristics such as small size and ability to cross the blood–brain barrier, as well as reduced immunogenicity and side effects. The use of a photosensitizer drug such as Verteporfin (BPD), in combination with a pan-vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI), Cediranib (CED), encapsulated in NPs will provide the medical field with new research on the possible ways to treat glioblastoma. Concomitant administration of BPD and CED NPs have the potential to induce dual photocytotoxic and cytostatic effects in U87 MG cells by (1) remotely triggering BPD through photodynamic therapy by irradiating laser at 690 nm and subsequent production of reactive oxygen species and (2) inhibiting cell proliferation by VEGFR interference and growth factor signaling mechanisms which may allow for longer progression free survival in patients and fewer systemic side effects. The specific aims of this research were to synthesize, characterize and assess cell viability and drug interactions for polyethylene-glycolated (PEGylated) polymeric based CED and BPD NPs which were less than 100 nm in size for enhanced permeation and retention effects. Synergistic effects were found using the co-administered therapies compared to the individual drugs. The major goal of this research was to investigate a new combination of photodynamic-chemotherapy drugs in nano-formulation for increased efficacy in glioblastoma treatment at reduced concentrations of therapeutics for enhanced drug delivery in vitro. Keywords: drug delivery; cancer; polymer; nanomedicine; angiogenesis; blood–brain barrier”

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Block-copolymers from PolySciTech used in the development of nano-emulsion based ultra-sound mediated noninvasive targeted drug delivery

Wednesday, November 14, 2018, 4:53 PM ET

Due to the circulatory nature of the human bloodstream, any agent introduced into the bloodstream at any location is quickly spread throughout the human body. This is good for drugs which need to be spread throughout the human body (i.e. systemic dosage) however is not very efficient for drugs whose location of action is only in one particular region. Researchers at Stanford University and Massachusetts General Hospital used several PEG-PCL, PEG-PLA, PEG-PLGA copolymers (Polyvivo AK073, AK001, AK052, AK090, AK004, and AK003) from PolySciTech (www.polyscitech.com) to generate nanoparticles with perfluorocarbons that could be activated using ultrasound. In this way the drug can be administered systemically but then released (uncaged) in the desired location of action. This research holds promise to enable targeted drug delivery with minimal side-effects. Read more: Zhong, Qian, Byung C. Yoon, Muna R. Aryal, Jeffrey B. Wang, Ananya Karthik, and Raag D. Airan. "Polymeric perfluorocarbon nanoemulsions are ultrasound-activated wireless drug infusion catheters." bioRxiv (2018): 315044. https://www.biorxiv.org/content/early/2018/09/10/315044.short

“Abstract: Catheter-based intra-arterial drug therapies have proven effective for a range of oncologic, neurologic, and cardiovascular applications. However, these procedures are limited by their invasiveness, as well as the relatively broad drug spatial distribution that is achievable with selective arterial catheterization. The ideal technique for local pharmacotherapy would be noninvasive and would flexibly deliver a given drug to any region of the body. Combining polymeric perfluorocarbon nanoemulsions with existent clinical focused ultrasound systems could in principle enable noninvasive targeted drug delivery, but it has not been clear whether these nanoparticles could provide the necessary drug loading, stability, and generalizability across a range of drugs to meet these needs, beyond a few niche applications. Here, we directly address all of those challenges and fully develop polymeric perfluorocarbon nanoemulsions into a generalized platform for ultrasound-targeted drug delivery with high potential for clinical translation. We demonstrate that a wide variety of drugs may be effectively uncaged with ultrasound using these nanoparticles, with drug loading increasing with hydrophobicity. We also set the stage for clinical translation by delineating production protocols that hew to clinical standards and yield stable and optimized ultrasound-activated drug-loaded nanoemulsions. Finally, as a new potential clinical application for these nanoemulsions, we exhibit their in vivo efficacy and performance for cardiovascular applications, by achieving local vasodilation in the highest flow vessel of the body, the aorta. This work establishes the power of polymeric perfluorocarbon nanoemulsions as a clinically-translatable platform for effective noninvasive ultrasonic drug uncaging for myriad targets in the brain and body.”

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PLGA from PolySciTech used in development of mixing system for rapid generation of nanoparticles

Wednesday, November 14, 2018, 4:53 PM ET

Nanoparticles are generally created by a controlled nanoprecipitation of polymer into a non-solvent. There are many different ways to generate nanoparticles which fundamentally differ mostly on how the mixing of polymer solution and non-solvent is accomplished. Recently, researchers at San Jose State University used PLGA (multiple types) from PolySciTech (www.polyscitech.com) to generate nanoparticles by a rapid and inexpensive technique using a 3D printed mixer. This research holds promise to enable rapid and simple creation of PLGA nanoparticles in a cost-effective manner. Read more: Le, Lan, Anuja Bokare, and Folarin Erogbogbo. "Hand Powered, cost effective, 3D printed nanoparticle synthesizer: Effects of polymer end caps, drugs, and solvents on lipid polymer hybrid nanoparticles." Materials Research Express (2018). http://iopscience.iop.org/article/10.1088/2053-1591/aaed72/meta

“Abstract: Lipid polymer hybrid nanoparticles (LPHNPs) consisting PLGA polymer as a core and DSPE-PEG as a lipid shell have been synthesized by nanoprecipitation method using hand powered, 3D printed Multi Inlet Vortex Mixer (MIVM). This method is relatively fast, simple and cost-effective as compared to other methods used for the synthesis of LPHNPs. Considering the importance of particle size in the nanoparticle mediated drug delivery, synthesis of LPHNPs with desired size has been attempted by examining various formulation variables. The synthesis conditions such as PLGA end caps, amount of drug and the type of organic solvent have been optimized to obtain LPHNPs of desired size. The formation of core-shell like structure of LPHNPs is confirmed by TEM analysis. The resulting LPHNPs were proven to have long term stability and controlled drug release properties.”

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PLGA from PolySciTech used in developing DP44mt loaded nanoparticles for cancer therapy against resistant cancers

Wednesday, November 14, 2018, 3:25 PM ET

DP44mt is a chelator molecule that binds iron and removes it from the intracellular environment. In cancer cells, this agent acts to induce cancer-cell death through upregulation of AMPK pathway and through corrupting autophagic mechanisms. One of the benefits of this therapeutic molecule is that it works against strains of cancers which are resistant to conventional chemotherapy. Recently, researchers at University of Houston purchase PLGA (AP041) from PolySciTech (www.polyscitech.com) for use in developing nanoparticles loaded with DP44mt. This research holds promise to provide for improved therapies against chemoresistant tumors. Read more: Holley, C. K., S. Alkhalifah, and S. Majd. "Fabrication and Optimization of Dp44mT-Loaded Nanoparticles." In 2018 40th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC), pp. 5733-5736. IEEE, 2018. https://ieeexplore.ieee.org/abstract/document/8513598/

“This paper describes the modulation of polymeric nanoparticle (NP) preparation to produce an optimal nanocarrier for delivery of the potent anti-tumor iron chelator, Di2-pyridylketone-4,4-dimethyl-3-thiosemicarbazone (Dp44mT) towards application in cancer therapy. We have previously shown the potential of poly (lactic-co-glycolic acid) (PLGA) NPs as a nano-carrier for delivery of Dp44mT to malignant cells. The focus of this study is to alter the fabrication parameters to improve the characteristics of these NPs as a delivery vehicle for Dp44mT. To this end, PLGA NPs encapsulating Dp44mT are fabricated using the nanoprecipitation method with systematic variations in (i) the amount of surfactant poly (vinyl alcohol) (PVA) in aqueous phase, and (ii) the drug to polymer ratio in organic phase. The resultant NPs are characterized for size, surface potential, encapsulation efficiency, and drug release profile. Results of this study showed that increasing the PVA % (within the examined range of 0.5-4% w/v) and decreasing the Dp44mT to PLGA ratio (within the tested range of 0.0375-0.3: 1 mg/mL) both led to an increase in drug encapsulation efficiency. Focusing on the optimal PVA percentage, we found that the changes in drug to polymer ratio did not have a significant impact on the size distribution and surface potential of Dp44mT-NPs and these NPs remained in the desirable range of 80-120 nm. Lastly, the release of Dp44mT from NPs differed for different Dp44mT: PLGA ratios, providing a means to further optimize the NP formulation for future cancer treatment applications. Keywords: Drugs, Encapsulation, Polymers, Cancer, Fabrication, Nanoparticles, Iron”

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Get ‘Bezwa-more’ for your Bezwada-branded product purchase placed through PolySciTech with discount code BEZWADA40

Thursday, November 8, 2018, 2:07 PM ET

In addition to in-house manufactured materials, PolySciTech also carries products by high-quality suppliers with a focus on biomedical and polymer products. Starting from November 8 through December 31, receive an additional 40% discount off the price of Bezwada-Brand products purchased through PolySciTech using the coupon code BEZWADA40. This includes the APB*** series of high molecular weight specialty polyesters for mechanically-demanding applications. Includes polymers of glycolide, caprolactone, dioxanone, lactide, trimethylene carbonate and other monomers with focus on mechanically robust products for implants, sutures, and other applications where strength and elasticity are paramount. Also included are the AEB*** series of Poly(ethylene glycol)-diacrylates are the ideal, cross-linkable hydrogel precursor for use in micropatterning, cell-scaffolds, and biological functions. Simply mixing these polymers with an appropriate solution of commercially available and biocompatible photo-initiator generates a liquid solution which readily forms into a solid gel upon exposure to UV light. Find these products with a competitive discount at www.polyscitech.com.

mPEG-PLA and PLA-PEG-COOH from PolySciTech used in the development of nanoparticles to treat colon cancer

Tuesday, November 6, 2018, 3:42 PM ET

Galbanic acid is a naturally occurring compound extracted from Ferula (wild carrots) which has potent activity against cancer, as well as anticoagulative, antiviral, and antibacterial properties. Despite its promising biological activity, it has very poor water solubility, which limits its clinical usefulness. Recently, researchers at Mashhad University of Medical Sciences (Iran) used mPEG-PLA (Cat# AK054) and PLA-PEG-COOH (Cat# AI030) from PolySciTech (www.polyscitech.com) to create galbanic-acid loaded nanoparticles. They assayed these particles against colorectal cancer and found promising results for efficacy against this form of cancer. This research holds promise for improved therapy against cancer with lower side-effects. Read more: Afsharzadeh, Maryam, Khalil Abnous, Rezvan Yazdian–Robati, Armin Ataranzadeh, Mohammad Ramezani, and Maryam Hashemi. "Formulation and evaluation of anticancer and antiangiogenesis efficiency of PLA–PEG nanoparticles loaded with galbanic acid in C26 colon carcinoma, in vitro and in vivo." Journal of cellular physiology (2018). https://onlinelibrary.wiley.com/doi/abs/10.1002/jcp.27346

“Abstract: Galbanic acid (GBA) is an active sesquiterpene coumarin derivative, with various medicinal benefits, including anticancer properties. However, the low solubility of GBA is the main limitation of its clinical applications. In this study, we used a nanosystem based on poly (D, l‐lactide)–polyethylene glycol (PLA–PEG), for the delivery of GBA to C26 colon carcinoma cells. The physicochemical characteristics of nanoparticles (NPs) prepared by the emulsification–evaporation method were evaluated. MTT assay was used to compare the anticell proliferation of GBA and PLA–PEG–GBA against C26 cell lines. PLA–PEG‐NPs with an average size of about 140 nm had an enhanced release of GBA at a pH of 5.5 compared with a pH of 7.4. Cytotoxicity studies showed that the IC 50 of the PLA–PEG–GBA NPs (8 µM) was significantly lower than free GBA (15 µM). In the in vivo study, PLA–PEG–GBA NPs exhibited remarkable efficacy and reduced in vivo toxicity in C26 colon carcinoma tumor‐bearing female BALB/c mice. To study the antiangiogenesis effect of the NPs, tumor sections were stained with an anti CD34 antibody. The results show the CD34 (+) vessels were decreased in the GBA and PLA–PEG–GBA treated mice by more than 75% and 90%, respectively. These results suggest that the encapsulation of GBA into the PLA–PEG could potentially be used for the treatment of colorectal cancer.”

PLGA from PolySciTech used in development of nanoparticle therapy against non-small cell lung cancer

Tuesday, October 30, 2018, 4:45 PM ET

Non-small cell lung cancer is an extremely common form of cancer, leading to more than 200,000 cases in USA per year. This type of cancer typically responds poorly to chemotherapy and often becomes resistant against many chemotherapeutics. Recently, researchers at Keck Graduate Institute, St. John's University, University of La Verne, and Harvard University used PLGA (PolyVivo AP082) from PolySciTech (www.polyscitech.com) to develop erlotinib loaded nanoparticles and tested these as a means to bypass NSCLC chemotherapy resistance. This research holds promise to provide for more effective treatments against this form of cancer. Read more: Vaidya, Bhuvaneshwar, Vineela Parvathaneni, Nishant S. Kulkarni, Snehal K. Shukla, Jenna K. Damon, Apoorva Sarode, Dipti Kanabar et al. "Cyclodextrin modified erlotinib loaded PLGA nanoparticles for improved therapeutic efficacy against non-small cell lung cancer." International Journal of Biological Macromolecules (2018). https://www.sciencedirect.com/science/article/pii/S0141813018338972

“Abstract: This study was aimed at developing a nanoparticle strategy to overcome acquired resistance against erlotinib in non-small cell lung cancer (NSCLC). To load erlotinib on biodegradable PLGA nanoparticles, erlotinib-cyclodextrin (Erlo-CD) complex was prepared using β-cyclodextrin sulfobutyl ether, which was in turn loaded in the core of PLGA nanoparticles using multiple emulsion solvent evaporation. Nanoparticles were characterized for size distribution, entrapment and loading efficiency, in-vitro release, and therapeutic efficacy against different lung cancer cells. Effect of formulation on cell cycle, apoptosis, and other markers was evaluated using flow cytometry and western blotting studies. The efficacy of optimized nanoformulation was evaluated using a clinically relevant in-vitro 3D-spheroid model. Results showed that Erlo-CD loaded nanoparticles (210 ± 8 nm in size) demonstrated 3-fold higher entrapment (61.5 ± 3.2% vs 21.9 ± 3.7% of plain erlotinib loaded nanoparticles) with ~5% loading efficiency and sustained release characteristics. Developed nanoparticles demonstrated significantly improved therapeutic efficacy against NSCLC cells in terms of low IC50 values and suppressed colony forming ability of cancer cells, increased apoptosis, and autophagy inhibition. Interestingly, 3D spheroid study demonstrated better anticancer activity of Erlo-CD nanoparticles compared to plain erlotinib. Present study has shown a premise to improve therapeutic efficacy against erlotinib-resistant lung cancer using modified nanoErlo formulations. Keywords: Erlotinib Sulfobutylether β-cyclodextrin complex Resistance lung cancer Autophagy 3D spheroids”

Fluorescent PLGA-rhodamine from PolySciTech used in development of siRNA nanoparticle therapy against glaucoma

Thursday, October 25, 2018, 3:39 PM ET

Glaucoma is a progressive disease which damages the eye’s optic nerves eventually leading to blindness if left untreated. The overgrowth of connective tissue (e.g. non-nerve based tissue for mechanical strength) is affiliated with the progression of this disease and silencing the genes associated with this may delay glaucoma’s progression. Recently, researchers at University Regensburg (Germany) used PLGA-rhodamine (PolyVivo AV011) from PolySciTech (www.polyscitech.com) as part of developing silencing RNA delivery nanoparticles as a potential therapy for glaucoma. This research holds promise to reduce blindness associated with this disease. Read more: Andrea E. Dillinger, Michaela Guter, Franziska Froemel, Gregor R. Weber, Kristin Perkumas, W. Daniel Stamer, Andreas Ohlmann, Rudolf Fuchshofer, Miriam Breunig “Intracameral Delivery of Layer‐by‐Layer Coated siRNA Nanoparticles for Glaucoma Therapy” Small 2018, 1803239. https://doi.org/10.1002/smll.201803239

“Abstract: Glaucoma is the second leading cause of blindness worldwide, often associated with elevated intraocular pressure. Connective tissue growth factor (CTGF) is a mediator of pathological effects in the trabecular meshwork (TM) and Schlemm's canal (SC). A novel, causative therapeutic concept which involves the intracameral delivery of small interfering RNA against CTGF is proposed. Layer‐by‐layer coated nanoparticles of 200–260 nm with a final layer of hyaluronan (HA) are developed. The HA‐coating should provide the nanoparticles sufficient mobility in the extracellular matrix and allow for binding to TM and SC cells via CD44. By screening primary TM and SC cells in vitro, in vivo, and ex vivo, the validity of the concept is confirmed. CD44 expression is elevated in glaucomatous versus healthy cells by about two‐ to sixfold. CD44 is significantly involved in the cellular uptake of HA‐coated nanoparticles. Ex vivo organ culture of porcine, murine, and human eyes demonstrates up to threefold higher accumulation of HA compared to control nanoparticles and much better penetration into the target tissue. Gene silencing in primary human TM cells results in a significant reduction of CTGF expression. Thus, HA‐coated nanoparticles combined with RNA interference may provide a potential strategy for glaucoma therapy.”

PLGA from PolySciTech used in creation of near-IR light responsive nanoparticles for cancer therapy

Thursday, October 25, 2018, 3:38 PM ET

Near-infrared light (wavelength between 700-1000 nm, for example T.V. remote control wavelength) has the ability to penetrate through human skin. Although this wavelength, by itself, has no therapeutic effect, it has the ability to trigger specifically designed responsive nanoparticles to cause certain events in a very tightly controlled location on the human body. Recently, researchers at Gwangju Institute of Science and Technology and Chonnam National University Medical School (Korea) utilized PLGA (PolyVivo AP036 and AP018) from PolySciTech (www.polyscitech.com) to create custom-fabricated nanoparticles which interact with NIR light to create heat and free-radicals. This technology holds promise for alternate cancer therapies based on sequential injection of nanoparticles and illumination of the tumor site. Read more: Thirunavukkarasu, Guru Karthikeyan, G. R. Nirmal, Hwangjae Lee, Mingyu Lee, Inkyu Park, and Jae Young Lee. "On-demand generation of heat and free radicals for dual cancer therapy using thermal initiator-and gold nanorod-embedded PLGA nanocomplexes." Journal of Industrial and Engineering Chemistry (2018). https://www.sciencedirect.com/science/article/pii/S1226086X18305227

“Abstract: Dual cancer therapy is an attractive strategy that can generate synergistic effects and also reduce drug-related side effects. Here, we developed multifunctional nanocomplexes capable of remote on-demand production of hyperthermia and free radicals in response to near infrared (NIR) light irradiation To this end, thermal initiator and gold nanorods were embedded in nano-sized temperature-responsive poly(lactic acid-co-glycolic acid). In vitro studies demonstrated controllable heat and radical production from the nanocomplexes with NIR and effective eradication of CT26 colon cancer cells with our nanocomplexes. Hence, our smart nanomaterial will potentially contribute precise and effective dual cancer treatment. Keywords Cancer therapy Nanomedicine Free radicals Photothermal Stimuli responsive material”

Website temporarily down

Saturday, October 20, 2018, 8:45 PM ET

October 20, 2018: akinainc.com and affiliated sites are down temporarily due to heavy winds in Indiana creating communications and power issues. We hope to have the issue resolved shortly.

mPEG-PLGA from PolySciTech used in research on immune checkpoint inhibitors for cancer therapy

Friday, October 19, 2018, 4:50 PM ET

One of the insidious features of cancer is that it has the ability to prevent the immune system from recognizing the diseased cells as ‘non-self.’ Immune checkpoint inhibitors, as chemotherapeutics, act to eliminate this feature of cancer and enable the immune system to attack it. Recently, researchers from Harvard Medical School, Hamad Bin Khalifa University (Qatar), and University of California, Los Angeles, used mPEG-PLGA (PolyVivo AK102) from PolySciTech (www.polyscitech.com) to develop anti-PD-1 loaded nanoparticles and investigated the effect of these nanoparticles on cancer therapy. This research holds promise for better understanding of immunotherapy cancer treatment options. read more: Farideh Ordikhani, Mayuko Uehara, Vivek Kasinath, Li Dai, Siawosh K. Eskandari, Baharak Bahmani, Merve Yonar, Jamil R. Azzi, Yousef Haik, Peter T. Sage, George F. Murphy, Nasim Annabi, Tobias Schatton, Indira Guleria, and Reza Abdi “Targeting antigen-presenting cells by anti–PD-1 nanoparticles augments antitumor immunity” JCI Insight. 2018;3(20):e122700 https://insight.jci.org/articles/view/122700

“Recent studies in cancer research have focused intensely on the antineoplastic effects of immune checkpoint inhibitors. While the development of these inhibitors has progressed successfully, strategies to further improve their efficacy and reduce their toxicity are still needed. We hypothesized that the delivery of anti–PD-1 antibody encapsulated in PLGA nanoparticles (anti–PD-1 NPs) to the spleen would improve the antitumor effect of this agent. Unexpectedly, we found that mice treated with a high dose of anti–PD-1 NPs exhibited significantly higher mortality compared with those treated with free anti–PD-1 antibody, due to the overactivation of T cells. Administration of anti–PD-1 NPs to splenectomized LT-α–/– mice, which lack both lymph nodes and spleen, resulted in a complete reversal of this increased mortality and revealed the importance of secondary lymphoid tissues in mediating anti–PD-1–associated toxicity. Attenuation of the anti–PD-1 NPs dosage prevented toxicity and significantly improved its antitumor effect in the B16-F10 murine melanoma model. Furthermore, we found that anti–PD-1 NPs undergo internalization by DCs in the spleen, leading to their maturation and the subsequent activation of T cells. Our findings provide important clues that can lead to the development of strategies to enhance the efficacy of immune checkpoint inhibitors.”

PLGA-PEG-COOH from PolySciTech used in development of nucleolin-targeting nanoparticles

Wednesday, October 17, 2018, 4:50 PM ET

Often, in cancer, nucleolin is overexpressed on the surface which allows it to be used as a target for drug-delivery. Recently, researchers at Tabriz University of Medical Sciences (Iran) utilized PLGA-PEG-COOH (PolyVivo AI076) from PolySciTech (www.polyscitech.com) to generate anti-nucleolin decorated nanoparticles for cancer targeting. This research holds promise for improved chemotherapeutics. Read more: Mosafer, Jafar, and Ahad Mokhtarzadeh. "Cell Surface Nucleolin as a Promising Receptor for Effective AS1411 Aptamer-Mediated Targeted Drug Delivery into Cancer Cells." Current drug delivery 15, no. 9 (2018): 1323-1329. https://www.ingentaconnect.com/contentone/ben/cdd/2018/00000015/00000009/art00013

“Background: One of the major abundant proteins in the nucleous is nucleolin that overexpressed on the cytoplasmic membrane of malignant and endothelial cells and makes it as a promising condidate for targeted drug delivery. Objectives: In this study, doxorubicin (Dox) as a chemotherapy drug was entrapped into the Poly lacticco- glycolic acid (PLGA)-based nanoparticles (NPs). Then, the targeting ability of anti nucleolin AS1411 aptamer-targeted Dox-encapsulated PLGA-based NPs (AS1411-NPs) was investigated in high nucleolin-expressing C26 colon carcinoma and rat C6 glioma cell lines compared with low nucleolin expressing mouse L929 cell line. Methods: We recently first assessed the existence of cell surface nucleolin of these three different cell lines by immunocytochemistry method. We found that a large amount of nucleolin was localized in the cytoplasmic membrane of C26 and C6 cell lines, with a very smaller amount on the surface of L929 cell line. Results: As a result, more rapidly internalization of AS1411-NPs into the C26 and C6 cells compared with L929 cells was verified. Conclusion: We think that AS1411-NPs, as a ligand, first bind to nucleolin, as a receptor, and then the receptor-ligand complex is more efficiently incorporated into the high nucleolin-expressing cell lines through receptor-mediated endocytosis pathway. Keywords: AS1411 aptamer; Nucleolin; PLGA; doxorubicin; internalization; targeted delivery”

mPEG-PLGA and PLGA from PolySciTech used in development of nanoparticle therapy for brain cancer

Tuesday, October 16, 2018, 4:03 PM ET

Glioblastoma is a common form of brain cancer which is typically fatal. The treatment of cancer requires the use of medicines that typically have very severe side-effects and a very narrow therapeutic window. Recently, a kinase inhibitor has shown promise for cancer therapy, however, it failed due to toxicity issues during phase 1 clinical trials. The ability to deliver this molecule in a more controlled manner may reduce the toxicity issues and allow for it to be used as a therapy. Recently, researchers from the University of Massachusetts and the Dana-Farber Cancer Institute used mPEG-PLGA (AK027) and PLGA (AP041) from PolySciTech (www.polyscitech.com) to create nanoparticles loaded with a novel kinase inhibitor as a prototype therapy for brain-cancer. These nanoparticles allow for dosing smaller concentrations in a more time-controlled manner. This research holds promise to provide for improved therapies against this fatal disease. Read more: Velpurisiva, Praveena, Brandon Piel, Jack Lepine, and Prakash Rai. "GSK461364A, a Polo-Like Kinase-1 Inhibitor Encapsulated in Polymeric Nanoparticles for the Treatment of Glioblastoma Multiforme (GBM)." Bioengineering 5, no. 4 (2018): 83. http://www.mdpi.com/2306-5354/5/4/83

“Abstract: Glioblastoma Multiforme (GBM) is a common primary brain cancer with a poor prognosis and a median survival of less than 14 months. Current modes of treatment are associated with deleterious side effects that reduce the life span of the patients. Nanomedicine enables site-specific delivery of active pharmaceutical ingredients and facilitates entrapment inside the tumor. Polo-like kinase 1 (PLK-1) inhibitors have shown promising results in tumor cells. GSK461364A (GSK) is one such targeted inhibitor with reported toxicity issues in phase 1 clinical trials. We have demonstrated in our study that the action of GSK is time dependent across all concentrations. There is a distinct 15-20% decrease in cell viability via apoptosis in U87-MG cells dosed with GSK at low concentrations (within the nanomolar and lower micromolar range) compared to higher concentrations of the drug. Additionally, we have confirmed that PLGA-PEG nanoparticles (NPs) containing GSK have shown significant reduction in cell viability of tumor cells compared to their free equivalents. Thus, this polymeric nanoconstruct encapsulating GSK can be effective even at low concentrations and could improve the effectiveness of the drug while reducing side effects at the lower effective dose. This is the first study to report a PLK-1 inhibitor (GSK) encapsulated in a nanocarrier for cancer applications. Keywords: GSK461364A; Glioblastoma Multiforme; polymeric nanoparticles; cytotoxicity; enhanced permeability and retention; polo-like kinase inhibitor; oncology; oncomedicine; U-87 MG”

PLA-PEG-PLA thermogel from PolySciTech used in recent patent on ocular controlled-release system

Wednesday, October 10, 2018, 12:25 PM ET

Delivery of medications into the ocular region is necessary for a wide range of diseases, but also challenging. Recently, researchers for Biohealthways, Inc. used PLA-PEG-PLA thermogel (PolyVivo AK100) from PolySciTech (www.polyscitech.com) in development of patent technology for delivery of ocular medicines. This research holds promise to treat a wide range of ocular diseases. Read more: Pan, David. "Biodegrading implantable ocular sustained release drug delivery system." U.S. Patent Application 15/924,318, filed September 20, 2018 .https://patents.google.com/patent/US20180264179A1/en

“Abstract: An ocular implant is provided for an intraocular delivery of a therapeutic biologic agent. The implant may be used intracamerally or intravitreally. The implant may include a sustained-release biodegradable core and a biodegradable shell, wherein the shell has a longer biodegradable half-life than the core. The core may include a biodegradable gel medium, an active therapeutic biologic agent, and a biologic stabilizer. Upon insertion into the anterior chamber or vitreous body of an eye, the therapeutic biologic agent is released over an extended period, that may range from one day to one year. The therapeutic biologic agent may be, for example, tissue-plasminogen activator, an anti-VEGF agent, or another biopharmaceutical. The biodegradable implant may completely dissolve after implantation and need not be removed.”

300th article! Mal-PEG-PLGA and mPEG-PLGA from PolySciTech used in development of immune-targeting nanoparticles to reduce organ rejection

Wednesday, October 10, 2018, 12:18 PM ET

Organ transplantation is a life-saving surgical technique in which the organs or tissues from a donor can be placed into a recipient to replace damaged or missing organs. Organ rejection occurs when the recipient’s immune system recognizes the transplanted organs or tissue as ‘non-self’ and launches an immune response against them. Recently researchers at Johns Hopkins University School of Medicine, Harvard Medical School, Tufts University, Universite de Lille (France), Hamad bin Khalifa University (Qatar), and University of Maryland used mPEG-PLGA (AK102) and Mal-PEG-PLGA (A110) from PolySciTech (www.polyscitech.com) to develop targeted nanoparticles to prevent immune-rejection of the transplanted tissue. This technology holds promise to prevent the potentially fatal incidence of tissue rejection. Furthermore, this article officially marks the 300th publication citing PolySciTech as the source of their research products since the first article published in 2011. Read more: Bahmani, Baharak, Mayuko Uehara, Liwei Jiang, Farideh Ordikhani, Naima Banouni, Takaharu Ichimura, Zhabiz Solhjou et al. "Targeted delivery of immune therapeutics to lymph nodes prolongs cardiac allograft survival." The Journal of clinical investigation 128, no. 11 (2018). https://www.jci.org/articles/view/120923

“The targeted delivery of therapeutic drugs to lymph nodes (LNs) provides an unprecedented opportunity to improve the outcomes of transplantation and immune-mediated diseases. The high endothelial venule is a specialized segment of LN vasculature that uniquely expresses peripheral node addressin (PNAd) molecules. PNAd is recognized by MECA79 mAb. We previously generated a MECA79 mAb–coated microparticle (MP) that carries tacrolimus. Although this MP trafficked to LNs, it demonstrated limited therapeutic efficacy in our transplant model. Here, we have synthesized a nanoparticle (NP) as a carrier of anti-CD3, and optimized the conjugation strategy to coat the NP surface with MECA79 mAb (MECA79-anti-CD3-NP) to enhance LN accumulation. As compared with nonconjugated NPs, a significantly higher quantity of MECA79-NPs accumulated in the draining lymph node (DLN). Many MECA79-NPs underwent internalization by T cells and dendritic cells within the LNs. Short-term treatment of murine cardiac allograft recipients with MECA79-anti-CD3-NP resulted in significantly prolonged allograft survival in comparison with the control groups. Prolonged graft survival following treatment with MECA79-anti-CD3-NP was characterized by a significant increase in intragraft and DLN Treg populations. Treg depletion abrogated the prolongation of heart allograft survival. We believe this targeted approach of drug delivery could redefine the methods of administering immune therapeutics in transplantation.”

These posts are syndicated from John Garner's blog at http://jgakinainc.blogspot.com/ where you can post a question or comment. (Load took 0.26954913139343 seconds)


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