Technical Blog
John GarnerJohn Garner, General Manager

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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mPEG-PLGA from PolySciTech used in research on the effect of LA:GA Sequencing

Tuesday, November 23, 2021, 8:42 AM ET

During the normal ring-opening polymerization of PLGA, the glycolide monomer typically reacts faster and more readily than the lactide monomer leading to non-random distribution of monomers along the polymer chain. This process competes with transesterification and other reactive processes in polymer manufacturing which act to improve randomness along the chain. Recently, researchers at Purdue University developed a novel method to make small quantities of mPEG-PLGA with precisely controlled monomer distribution. They used mPEG-PLGA (Cat# AK010) from PolySciTech (www.polyscitech.com) (manufactured using conventional bulk-melt ring-opening polymerization) to compare the various batches they had made. In addition to traditional PLGA offerings, Akina has recently begun adding products of PLGA alternating LA:GA based on 3-methylglycolide monomer (e.g. cat# AP279 – AP281). This research holds promise to provide a more mechanistic understanding of PLGA sequencing effect on the polymer properties. Read more: Yoo, Jin, Dhushyanth Viswanath, and You-Yeon Won. "Strategy for Synthesis of Statistically Sequence-Controlled Uniform PLGA and Effects of Sequence Distribution on Interaction and Drug Release Properties." ACS Macro Letters 10 (2021): 1510-1516. https://pubs.acs.org/doi/abs/10.1021/acsmacrolett.1c00637

“Extensive studies have been conducted to elucidate the effects of such parameters as molecular weight, polydispersity, and composition on the controlled release properties of poly(d,l-lactic-co-glycolic acid) (PLGA). However, studies dealing with the effect of monomer sequence distribution have been sparse mainly because of the difficulty of precisely controlling the monomer sequence in PLGA. Herein, we present a semibatch copolymerization strategy that enables the production of statistically sequence-controlled “uniform PLGA” polymers through control of the rate of comonomer addition. Using this method, a series of PEG–PLGA samples having a comparable molecular weight and composition but different sequence distributions (uniform vs gradient) were prepared. The properties of these materials (PEG crystallization/melting, hygroscopicity, aqueous sol–gel transition, drug release kinetics) were found to significantly vary, demonstrating that sequence control only at the statistical level still significantly influences the properties of PLGA. Most notably, uniform PLGA exhibited the more sustained drug release behavior compared to gradient PLGA.”

PLGA-PEG-COOH from PolySciTech used in development of carborane-loaded nanoparticles for prostate cancer treatment

Tuesday, November 16, 2021, 4:31 PM ET

PSMA is a marker which is overexpressed on cancer cells and can provide an attractive target for ligand-based therapies. Recently researchers at University of California San Francisco used PLGA-PEG-COOH (cat# AI078) from PolySciTech (www.polyscitech.com) to create PSMA-targetting nanoparticles loaded with carborane for boron neutron capture therapy against prostate cancer. This research holds promise to improve therapeutic options for cancer. Read more: Meher, Niranjan, Kyounghee Seo, Sinan Wang, Anil P. Bidkar, Miko Fogarty, Suchi Dhrona, Xiao Huang et al. "Synthesis and Preliminary Biological Assessment of Carborane-Loaded Theranostic Nanoparticles to Target Prostate-Specific Membrane Antigen." ACS Applied Materials & Interfaces (2021). https://pubs.acs.org/doi/abs/10.1021/acsami.1c16383

“Boron neutron capture therapy (BNCT) is an encouraging therapeutic modality for cancer treatment. Prostate-specific membrane antigen (PSMA) is a cell membrane protein that is abundantly overexpressed in prostate cancer and can be targeted with radioligand therapies to stimulate clinical responses in patients. In principle, a spatially targeted neutron beam together with specifically targeted PSMA ligands could enable prostate cancer-targeted BNCT. Thus, we developed and tested PSMA-targeted poly(lactide-co-glycolide)-block-poly(ethylene glycol) (PLGA-b-PEG) nanoparticles (NPs) loaded with carborane and tethered to the radiometal chelator deferoxamine B (DFB) for simultaneous positron emission tomography (PET) imaging and selective delivery of boron to prostate cancer. Monomeric PLGA-b-PEGs were covalently functionalized with either DFB or the PSMA ligand ACUPA. Different nanoparticle formulations were generated by nanoemulsification of the corresponding unmodified and DFB- or ACUPA-modified monomers in varying percent fractions. The nanoparticles were efficiently labeled with 89Zr and were subjected to in vitro and in vivo evaluation. The optimized DFB(25)ACUPA(75) NPs exhibited strong in vitro binding to PSMA in direct binding and competition radioligand binding assays in PSMA(+) PC3-Pip cells. [89Zr]DFB(25) NPs and [89Zr]DFB(25)ACUPA(75) NPs were injected to mice with bilateral PSMA(−) PC3-Flu and PSMA(+) PC3-Pip dual xenografts. The NPs demonstrated twofold superior accumulation in PC3-Pip tumors to that of PC3-Flu tumors with a tumor/blood ratio of 25; however, no substantial effect of the ACUPA ligands was detected. Moreover, fast release of carborane from the NPs was observed, resulting in a low boron delivery to tumors in vivo. In summary, these data demonstrate the synthesis, characterization, and initial biological assessment of PSMA-targeted, carborane-loaded PLGA-b-PEG nanoparticles and establish the foundation for future efforts to enable their best use in vivo.”

PLGA-NH2 from PolySciTech used in testing nanoparticles for platinum-based anticancer therapy

Tuesday, November 16, 2021, 4:29 PM ET

Cisplatin is the first FDA approved metal-based drug for treatment of solid tumors as it uses platinum as an active agent. In the blood stream, however, it reacts with glutathione which diminishes its effectiveness. Recently, researchers at City University of New York used PLGA-NH2 (AI010) to make Cy5.5 labeled nanoparticles for tracking purposes as part of their research in making nanoparticles for delivery of cisplatin. This research holds promise for improving treatments against cancer. Read more: Marek T. Wlodarczyk “Enhanced Platinum (II) Drug Delivery for Anti-cancer Therapy” PhD Dissertation City University of New York, 2021 https://academicworks.cuny.edu/cgi/viewcontent.cgi?article=5668&context=gc_etds

“Over the years, anti-cancer therapies have improved the overall survival rate of patients. Nevertheless, the traditional free drug therapies still suffer from side effects and systemic toxicity, resulting in low drug dosages in the clinic. This often leads to suboptimal drug concentrations reaching cancer cells, contributing to treatment failure and drug resistance. Among available anticancer therapies, metallodrugs are of great interest. Platinum (II)-based agents are highly potent and are used to treat many cancers, including ovarian cancer (OC). Cisplatin (cisdiaminedichloroplatinum (II)) is the first Food and Drug Administration (FDA)-approved metallodrug for treatment of solid tumors, and its mechanism of action is based on inhibition of cancer cell replication via binding to nuclear DNA. However, circulating cisplatin binds to glutathione and other proteins in the blood compartment, diminishing the concentration of the free drug available for therapy. Also, highly potent cisplatin is associated with severe side effects, limiting the dosage of Pt(II) that can be administered in the clinic. The next generation Pt(II) drugs aim at sustaining the same effectiveness while improving systemic toxicity. Carboplatin is a second-generation Pt-based agent approved by the Food and Drug Administration (FDA). Slower hydrolysis times for carboxylate ligands in carboplatin, compared to rather fast times for chlorine ligands in cisplatin, lead to longer blood circulation times and lesser side effects. The therapeutic effect of carboplatin is comparable with cisplatin in some tumors, but it requires higher drug dosages, and the survival rate did not improve.”

PLGA from PolySciTech used in development of technetium-loaded nanoparticles for theranostic applications

Thursday, October 28, 2021, 8:47 AM ET

The primary benefit and complication of nanoparticles is that they are small. The same diminutive size which allows them to flow freely through the circulatory system also makes their detection and localization difficult. Recently, researchers at University of Rome (Italy) used PLGA (Cat# AP045) from PolySciTech (www.polyscitech.com) to create technetium-labelled nanoparticles. These radio-labelled nanoparticles enabled discrete and accurate imaging of the localization of particles in an animal model. This research holds promise to improve nanobased therapies against several disease states including cancer. Read More: Varani, Michela, Giuseppe Campagna, Valeria Bentivoglio, Matteo Serafinelli, Maria Luisa Martini, Filippo Galli, and Alberto Signore. "Synthesis and Biodistribution of 99mTc-Labeled PLGA Nanoparticles by Microfluidic Technique." Pharmaceutics 13, no. 11 (2021): 1769. https://www.mdpi.com/1999-4923/13/11/1769

“The aim of present study was to develop radiolabeled NPs to overcome the limitations of fluorescence with theranostic potential. Synthesis of PLGA-NPs loaded with technetium-99m was based on a Dean-Vortex-Bifurcation Mixer (DVBM) using an innovative microfluidic technique with high batch-to-batch reproducibility and tailored-made size of NPs. Eighteen different formulations were tested and characterized for particle size, zeta potential, polydispersity index, labeling efficiency, and in vitro stability. Overall, physical characterization by dynamic light scattering (DLS) showed an increase in particle size after radiolabeling probably due to the incorporation of the isotope into the PLGA-NPs shell. NPs of 60 nm (obtained by 5:1 PVA:PLGA ratio and 15 mL/min TFR with 99mTc included in PVA) had high labeling efficiency (94.20 ± 5.83%) and > 80% stability after 24 h and showed optimal biodistribution in BALB/c mice. In conclusion, we confirmed the possibility of radiolabeling NPs with 99mTc using the microfluidics and provide best formulation for tumor targeting studies. Keywords: radiolabeled nanoparticles; poly (lactic-co-glycolic acid) (PLGA); nuclear medicine; microfluidics”

PLGA from PolySciTech used in research on 3D printed graphene based on a temporary nickel scaffold

Thursday, October 28, 2021, 8:47 AM ET

Typically, the biodegradability of PLGA is utilized in a medical sense to create structures which slowly break down over time in the human body in a non-toxic manner for tissue engineering or drug-delivery applications. PLGA’s degradation, however, is hydrolysis and occurs in general upon contact with any water proceeding faster in acid or alkali conditions. This allows PLGA to be used in engineering applications as a temporary structure. Recently, researchers at University of Cincinnati and A&T North Carolina State University used PLGA (PolyVivo cat# AP234) from PolySciTech (www.polyscitech.com) as a temporary binder for nickel particles as part of development of a novel 3D-printed catalyst system for graphene structure creation. This research holds promise to improve capabilities of forming complex structures from reinforced materials. Read more: Kondapalli, Vamsi Krishna Reddy, Xingyu He, Mahnoosh Khosravifar, Safa Khodabakhsh, Boyce Collins, Sergey Yarmolenko, Ashley Paz y Puente, and Vesselin Shanov. "CVD Synthesis of 3D-Shaped 3D Graphene Using a 3D-Printed Nickel–PLGA Catalyst Precursor." ACS Omega (2021). https://pubs.acs.org/doi/abs/10.1021/acsomega.1c04072

“Earlier, various attempts to develop graphene structures using chemical and nonchemical routes were reported. Being efficient, scalable, and repeatable, 3D printing of graphene-based polymer inks and aerogels seems attractive; however, the produced structures highly rely on a binder or an ice support to stay intact. The presence of a binder or graphene oxide hinders the translation of the excellent graphene properties to the 3D structure. In this communication, we report our efforts to synthesize a 3D-shaped 3D graphene (3D2G) with good quality, desirable shape, and structure control by combining 3D printing with the atmospheric pressure chemical vapor deposition (CVD) process. Direct ink writing has been used in this work as a 3D-printing technique to print nickel powder–PLGA slurry into various shapes. The latter has been employed as a catalyst for graphene growth via CVD. Porous 3D2G with high purity was obtained after etching out the nickel substrate. The conducted micro CT and 2D Raman study of pristine 3D2G revealed important features of this new material. The interconnected porous nature of the obtained 3D2G combined with its good electrical conductivity (about 17 S/cm) and promising electrochemical properties invites applications for energy storage electrodes, where fast electron transfer and intimate contact with the active material and with the electrolyte are critically important. By changing the printing design, one can manipulate the electrical, electrochemical, and mechanical properties, including the structural porosity, without any requirement for additional doping or chemical postprocessing. The obtained binder-free 3D2G showed a very good thermal stability, tested by thermo-gravimetric analysis in air up to 500 °C. This work brings together two advanced manufacturing approaches, CVD and 3D printing, thus enabling the synthesis of high-quality, binder-free 3D2G structures with a tailored design that appeared to be suitable for multiple applications.”

PEG-PLA from PolySciTech used in development of galbanic-acid based colon-cancer therapy

Monday, October 25, 2021, 1:17 PM ET

PEG-PLA from PolySciTech used in development of galbanic-acid based colon-cancer therapy

Galbanic acid (compound extracted from Asafoetida herb) has demonstrated apoptotic activity against cancer cells in the past. Recently, researchers at Mashhad University of Medical Sciences utilized PEG-PLA (PolyVivo cat# AK054) to create galbanic acid-loaded nanoparticles. They tested these for efficacy and safety both in-vitro as well as in an in-vivo model. This research may provide for improved treatments of colon cancer in the future. Read more: Hashemi, Maryam, Maryam Afsharzadeh, Maryam Babaei, Mahboubeh Ebrahimian, Khalil Abnous, and Mohammad Ramezani. "Enhanced anticancer efficacy of docetaxel through galbanic acid encapsulated into PLA-PEG nanoparticles in treatment of colon cancer, in vitro and in vivo study." Journal of Bioactive and Compatible Polymers (2021): 08839115211053922. https://journals.sagepub.com/doi/abs/10.1177/08839115211053922

“Abstract: Cancer is one of the most leading causes of human mortality and despite outstanding breakthrough in introducing new therapeutic approaches, the clinical outcomes are disappointing. Therefore, extensive research in design and preparation of more efficient drug delivery systems can open a window to shine light into the therapeutic modality. In this study, we evaluated the effect of galbanic acid (GBA) encapsulated into PLA-PEG nanoparticles (NPs) to enhanced anticancer efficacy of docetaxel (DOC) for the treatment of colon cancer. Prepared NPs were characterized by different methods in terms of size, zeta potential, and drug loading capacity. MTT assay was used to investigate the anti-proliferation of GBA-loaded PEG-PLA NPs along with DOC. The therapeutic efficacy of PEG-PLA@GBA NPs & DOC was further investigated in C26 tumor-bearing BALB/c mice model. The resulting NPs were narrowly distributed (PDI = 0.06) with the mean diameter of 148 ± 9 nm with somewhat negative charge. GBA were efficiently loaded into mPEG-PLA NPs with encapsulation efficiency of about 40% ± 3. Cytotoxicity studies showed that NPs loaded with GBA and fixed concentration of docetaxel (20 nM) have higher toxicity (IC50 = 6 ± 1.8 µM) than either PEG-PLA@GBA (IC50 = 8 ± 1.2 µM) or free GBA (IC50 = 15 ± 3.5 µM) in C26 cells. In vivo studies revealed a synergistic effect of PEG-PLA@GBA NPs and DOC on tumor growth inhibition and survival rate in comparison with monotherapy approach. Keywords: Galbanic acid, docetaxel, PEG-PLA nanoparticles, colon cancer, combination therapy”

PLGA from PolySciTech used in development of microelectrode array for non-opioid pain management

Tuesday, October 5, 2021, 10:55 AM ET

Current pain management strategies typically rely on opioid medications which have a high propensity to lead to addiction. Opioid addiction has become a world-wide societal problem in recent years requiring research into opioid-free pain relief strategies. Recently, researchers at University of Washington used mPEG-PLGA (Cat# AK106) and PLGA (Cat# AP045) from PolySciTech (www.polyscitech.com) to create curcumin-loaded nanoparticles as part of development of nanoparticle loaded microelectrode array for pain management. This research holds promise to improve pain management strategies in the future. Read more: Xu, Nuo. "Nanoparticle loaded implantable flexible microelectrode arrays for pain management after spinal cord surgery." PhD diss., University of Washington, 2021. https://search.proquest.com/openview/530e9f32e470658b868b55aabf7b6312/1?pq-origsite=gscholar&cbl=18750&diss=y

“Abstract: The health care system currently faces significant burden with abuse of opioids and an unmet market need for pain management after surgery and injury. A drug delivery device that can improve drug delivery efficiency, increase drug duration of action, and deliver anesthetics topically with low toxicity is needed. Implantable flexible microelectrode arrays are widely used after spinal cord injury for pain mainagement, but they have limitations in improving the solubility, bioavailability, and permeability of drug. Biodegradable polymeric nanoparticles have highly tailorable physicochemical properties, and with incorporation on microelectrode arrays (MEAs), may increase the physical and chemical properties of therapeutic agents such as permeability, solubility and bioavailability. However, drug-loaded biodegradable nanoparticle-polypyrrole coated MEA for drug delivery has not been reported in literature. Therefore, we investigate the use of biodegradable nanoparticles for controlled release of bupivacaine hydrochloride from MAEs for pain management following spinal cord surgery. Bupivacaine hydrochloride, a commonly used FDA-approved anesthetic, is chosen as the model drug due to its nerve block and anti-inflammatory effects. This work starts with the exploration of the relationship between the formulation parameters of biodegradable nanoparticles and their physicochemical properties. Then, the bupivacaine hydrochloride loaded nanoparticles are formulated, and the drug loading of the nanoparticles is explored through iterating formulation parameters. Thereafter, nanoparticles with different surface charges are loaded on the MAEs to determine the relationship between the surface charge of nanoparticles and the release behavior of these nanoparticles. Finally, the release behavior of the nanoparticles from the MAEs is used as a guide to further optimize the bupivacaine hydrochloride loaded nanoparticle formulation.”

PLA from PolySciTech used in development of Doxycycline/miR-21i co-delivery nanoparticle for cancer treatment

Monday, September 27, 2021, 3:00 PM ET

One potential method for treatment of cancer is by reducing the amount of microRNA that the cancer can produce in addition to conventional chemotherapy. Recently, researchers at University of Cincinnati used PLA (AP128) from PolySciTech to create multi-drug loaded nanoparticles. This treatment holds promise to improve therapy against cancer. Rear more: Sriram, Vishnu, and Joo-Youp Lee. "Calcium Phosphate-Polymeric Nanoparticle System for Co-delivery of microRNA-21 Inhibitor and Doxorubicin." Colloids and Surfaces B: Biointerfaces (2021): 112061. https://www.sciencedirect.com/science/article/abs/pii/S0927776521005051

“Highlights: NPs successfully achieved sequential delivery of miR-21 inhibitor followed by Dox. NPs delivered miR-21 inhibitor to the cytoplasm through endosomal escape. NPs downregulated miR-21 levels and upregulated PTEN levels. Abstract: NPs showed enhanced cytotoxicity against MDA-MB-231 and A549 cells. Abstract: Targeted combination therapy has shown promise to achieve maximum therapeutic efficacy by overcoming drug resistance. MicroRNA-21 (miR-21) is frequently overexpressed in various cancer types including breast and non-small cell lung cancer and its functions can be inhibited by miR inhibitor (miR-21i). A combination of miR-21i and a chemo drug, doxorubicin (Dox), can provide synergistic effects. Here, we developed a calcium phosphate (CaP)-coated nanoparticle (NP) formulation to co-deliver miR-21i along with Dox. This NP design can be used to deliver the two agents with different physiochemical properties. The NP formulation was optimized for particle size, polydispersity, Dox loading, and miR-21i loading. The NP formulation was confirmed to downregulate miR-21 levels and upregulate tumor suppressor gene levels. The cytotoxic efficacy of the combined miR-21i and Dox-containing NPs was found to be higher than that of Dox. Therefore, the CaP-coated hybrid lipid-polymeric NPs hold potential for the delivery of miR-21i and Dox. Keywords: Polymeric nanoparticles Calcium phosphate microRNA-21 inhibitor Doxorubicin Co-delivery Combination therapy”

mPEG-PLGA from PolySciTech used in development of microfluidic nanoparticles for delivery of peptides

Friday, September 24, 2021, 4:10 PM ET

Peptides represents an important and useful class of drugs which are limited due to their rapid breakdown in the blood stream. Recently researchers from The University of Queensland, National Center for Nanoscience and Technology, and Southern University of Science and Technology (China), mPEG-PLGA (Cat# AK026) from PolySciTech (www.polyscitech.com) was used for peptide delivery. This research holds promise to improve the longevity of peptide drugs thus extending their usefulness. Read More: Han, Felicity Y., Weizhi Xu, Vinod Kumar, Cedric S. Cui, Xaria Li, Xingyu Jiang, Trent M. Woodruff, Andrew K. Whittaker, and Maree T. Smith. "Optimisation of a Microfluidic Method for the Delivery of a Small Peptide." Pharmaceutics 13, no. 9 (2021): 1505. https://www.mdpi.com/1276894

“Abstract: Peptides hold promise as therapeutics, as they have high bioactivity and specificity, good aqueous solubility, and low toxicity. However, they typically suffer from short circulation half-lives in the body. To address this issue, here, we have developed a method for encapsulation of an innate-immune targeted hexapeptide into nanoparticles using safe non-toxic FDA-approved materials. Peptide-loaded nanoparticles were formulated using a two-stage microfluidic chip. Microfluidic-related factors (i.e., flow rate, organic solvent, theoretical drug loading, PLGA type, and concentration) that may potentially influence the nanoparticle properties were systematically investigated using dynamic light scattering and transmission electron microscopy. The pharmacokinetic (PK) profile and biodistribution of the optimised nanoparticles were assessed in mice. Peptide-loaded lipid shell-PLGA core nanoparticles with designated size (~400 nm) and a sustained in vitro release profile were further characterized in vivo. In the form of nanoparticles, the elimination half-life of the encapsulated peptide was extended significantly compared with the peptide alone and resulted in a much higher distribution into the lung. These novel nanoparticles with lipid shells have considerable potential for increasing the circulation half-life and improving the biodistribution of therapeutic peptides to improve their clinical utility, including peptides aimed at treating lung-related diseases. Keywords: drug delivery system; nanoparticles; poly (lactic-co-glycolic acid) (PLGA); microfluidic; pharmacokinetics (PK) and biodistribution”

PLGA from PolySciTech Used in development of intracellular delivery systems.

Friday, September 24, 2021, 4:09 PM ET

The ability to deliver medicines and genetic materials into a cell can be a powerful tool to treat disease. Recently, researchers at University of Connecticut and University of Iowa purchased PLGA from PolySciTech (www.polyscitech.com) to create poly(histidine)-PLGA mixed nanoparticles. They researched the use of this as a way to deliver nanoparticles into cells. This research holds promise to improve intracellular delivery. Read more: Wahane, Aniket, Shipra Malik, Kuo-Chih Shih, Ravinder Reddy Gaddam, Chaohao Chen, Yun Liu, Mu-Ping Nieh, Ajit Vikram, and Raman Bahal. "Dual-Modality Poly-l-histidine Nanoparticles to Deliver Peptide Nucleic Acids and Paclitaxel for In Vivo Cancer Therapy." ACS Applied Materials & Interfaces (2021). https://pubs.acs.org/doi/abs/10.1021/acsami.1c11981

“Abstract: Cationic polymeric nanoformulations have been explored to increase the transfection efficiency of small molecules and nucleic acid-based drugs. However, an excessive positive charge density often leads to severe cell and tissue-based toxicity that restricts the clinical translation of cationic polymeric nanoformulations. Herein, we investigate a series of cationic poly(lactic-co-glycolic acid) (PLGA)-histidine-based nanoformulations for enhanced cytoplasmic delivery with minimal toxicity. PLGA/poly-l-histidine nanoparticles show promising physico-biochemical features and transfection efficiency in a series of in vitro and cell culture-based studies. Further, the use of acetone/dichloromethane as a solvent mixture during the formulation process significantly improves the morphology and size distribution of PLGA/poly-l-histidine nanoparticles. PLGA/poly-l-histidine nanoformulations undergo clathrin-mediated endocytosis. A contrast-matched small-angle neutron scattering experiment confirmed poly-l-histidine’s distribution on the PLGA nanoformulations. PLGA/poly-l-histidine formulations containing paclitaxel as a small molecule-based drug and peptide nucleic acids targeting microRNA-155 as nucleic acid analog are efficacious in in vitro and in vivo studies. PLGA/poly-l-histidine NPs significantly decrease tumor growth in PNA-155 (∼6 fold) and paclitaxel (∼6.5 fold) treatment groups in a lymphoma cell line derived xenograft mice model without inducing any toxicity. Hence, PLGA/poly-l-histidine nanoformulations exhibit substantial transfection efficiency and are safe to deliver reagents ranging from small molecules to synthetic nucleic acid analogs and can serve as a novel platform for drug delivery. KEYWORDS: poly-l-histidine PLGA nanoparticles proton-sponge effect microRNAs”

PLGA from PolySciTech used in development of Long-Acting implant for vaccination against Covid-19 variants

Thursday, September 16, 2021, 2:32 PM ET

The way in which an antigen or other structure is presented to the immune system has an effect on how strong the immune system develops a response against that particular antigen. Notably, for vaccination, it is optimal to provide an antigen to the immune system over an extended time to maximize vaccine efficacy. Recently, researchers at University of California, San Diego loaded antigens that are conserved between variants of concern (i.e. similar antigen structures that show up in multiple viral variants despite their other differences) into a PLGA/PEG rod extrusion mix comprised of PLGA (cat# AP041) from PolySciTech (www.polyscitech.com) to create a slow-release antigen rod which was both stable at room temperature and eliminated the need for follow-up innoculations. This research holds promise for improving protections against both the current pandemic as well as future pandemic’s yet to come. Read more: Ortega-Rivera, Oscar A., Matthew D. Shin, Angela Chen, Veronique Beiss, Miguel A. Moreno-Gonzalez, Miguel A. Lopez-Ramirez, Maria Reynoso et al. "Trivalent Subunit Vaccine Candidates for COVID-19 and Their Delivery Devices." Journal of the American Chemical Society (2021). https://pubs.acs.org/doi/abs/10.1021/jacs.1c06600

“The COVID-19 pandemic highlights the need for platform technologies enabling rapid development of vaccines for emerging viral diseases. The current vaccines target the SARS-CoV-2 spike (S) protein and thus far have shown tremendous efficacy. However, the need for cold-chain distribution, a prime-boost administration schedule, and the emergence of variants of concern (VOCs) call for diligence in novel SARS-CoV-2 vaccine approaches. We studied 13 peptide epitopes from SARS-CoV-2 and identified three neutralizing epitopes that are highly conserved among the VOCs. Monovalent and trivalent COVID-19 vaccine candidates were formulated by chemical conjugation of the peptide epitopes to cowpea mosaic virus (CPMV) nanoparticles and virus-like particles (VLPs) derived from bacteriophage Qβ. Efficacy of this approach was validated first using soluble vaccine candidates as solo or trivalent mixtures and subcutaneous prime-boost injection. The high thermal stability of our vaccine candidates allowed for formulation into single-dose injectable slow-release polymer implants, manufactured by melt extrusion, as well as microneedle (MN) patches, obtained through casting into micromolds, for prime-boost self-administration. Immunization of mice yielded high titers of antibodies against the target epitope and S protein, and data confirms that antibodies block receptor binding and neutralize SARS-CoV and SARS-CoV-2 against infection of human cells. We present a nanotechnology vaccine platform that is stable outside the cold-chain and can be formulated into delivery devices enabling single administration or self-administration. CPMV or Qβ VLPs could be stockpiled, and epitopes exchanged to target new mutants or emergent diseases as the need arises.”

PLGA from PolySciTech used in bacteria-mediated drug-delivery system development

Wednesday, September 15, 2021, 2:52 PM ET

There are many ways to make drug-delivery systems and for operating at such small-scale often it is advantageous to employ microorganisms to help with this. Recently, researchers at Virginia Tech used PLGA (Cat# AP082) from PolySciTech (www.polyscitech.com) to create bacteria-attaching nanobeads for using the bacteria to help deliver drug molecules. This research represents a novel paradigm in drug-delivery technologies. Read more: Zhan, Ying, Austin Fergusson, Lacey R. McNally, Richey M. Davis, and Bahareh Behkam. "Robust and Repeatable Biofabrication of Bacteria-Mediated Drug Delivery Systems: Effect of Conjugation Chemistry, Assembly Process Parameters, and Nanoparticle Size." Authorea Preprints (2021). https://www.authorea.com/doi/full/10.22541/au.163100509.93917936

“Abstract: Bacteria-mediated drug delivery systems comprising nanotherapeutics conjugated onto bacteria synergistically augment the efficacy of both therapeutic modalities in cancer therapy. Nanocarriers preserve therapeutics' bioavailability and reduce systemic toxicity, while bacteria selectively colonize the cancerous tissue, impart intrinsic and immune-mediated antitumor effects, and propel nanotherapeutics interstitially. The optimal bacteria-nanoparticle (NP) conjugates would carry the maximal NP load with minimal motility speed hindrance for effective interstitial distribution. Furthermore, a well-defined and repeatable NP attachment density distribution is crucial to determining these biohybrid systems' efficacious dosage and robust performance. Herein, we utilized our Nanoscale Bacteria-Enabled Autonomous Delivery System (NanoBEADS) platform to investigate the effects of assembly process parameters of mixing method, volume, and duration on NP attachment density and repeatability. We also evaluated the effect of linkage chemistry and NP size on NP attachment density, viability, growth rate, and motility of NanoBEADS. We show that the linkage chemistry impacts NP attachment density while the self-assembly process parameters affect the repeatability and, to a lesser extent, attachment density. Lastly, the attachment density affects NanoBEADS' growth rate and motility in an NP size-dependent manner. These findings will contribute to the development of scalable and repeatable bacteria-nanoparticle biohybrids for applications in drug delivery and beyond.”

PEG-PLGA from PolySciTech used in development of Boron Neutron capture therapy to treat prostate cancer

Wednesday, September 15, 2021, 2:51 PM ET

One therapy for cancer is to apply targeted radiation treatment to remove the tumor that route. To do this a sensitizer or comparable compound is loaded into a targeted system designed to specifically accumulate in the tumor site. Then the area is affected by a relatively inert force (such as low-energy neutrons) to induce a radioactive response. Recently, researchers at UCSF purchased PEG-PLGA (cat# AK037) and PLGA-PEG-COOH (cat# AI078) from PolySciTech (www.polyscitech.com) to create nanoparticles loaded with boron for delivery to prostate cancers. This enables treatment of the cancer by exposing the area to neutrons which then cause the boron to emit alpha radiation in a localized manner. This research holds promise to improve therapeutic options against difficult cancers in the future. Read more: Dhrona, Suchi. "Development of PSMA Targeted Polymer Nanoparticles to Treat Prostate Cancer By Boron Neutron Capture Therapy Directed Against PSMA." PhD diss., UCSF, 2021. https://escholarship.org/content/qt6c6292zv/qt6c6292zv.pdf

“Prostate-specific membrane antigen (PSMA) is a cell surface enzyme highly over expressed in prostate cancer cells that can be employed as a target for prostate cancer imaging and drug delivery. Boron Neutron Capture Therapy (BNCT) is an emerging noninvasive therapeutic modality for treating locally invasive malignant tumors by selective delivery of high boron content to the tumour and then subjecting the tumour to epithermal neutron beam radiation. In this study, we develop carborane encapsulated amphiphilic polymer nanoparticles by conjugating urea based PSMA inhibitors (ACUPA) and 89Zr chelating deferoxamine B (DFB) ligand and have investigated their efficacy to deliver enhanced boron payload to PSMA positive prostate cancer cells with simultaneous positron emission tomography (PET) imaging . Three different carborane encapsulated PLGA-b-PEG nanoparticles (NPs) were formulated with and without the PSMA targeting ligand, out of which two selected formulations; DFB(25)ACUPA(75) NPs and DFB(25) NPs radiolabelled with 89Zr were administered to mice bearing dual PSMA(+) PC3-Pip and PSMA(-) PC3-Flu xenografts. PET imaging and biodistribution studies were performed to demonstrate the in vivo uptake in mice. The NPs showed 2-fold higher uptake in PSMA(+) PC3-Pip tumors to that of PSMA(-) PC3-Flu tumors with a very high tumor/blood ratio of 20. However, no significant influence of the ACUPA ligands were observed. Additionally, the NPs demonstrated fast release of carborane with low delivery of boron to tumors in vivo. Although the in vivo afficacy of those NPs remain limited, a significant progress towards the synthesis, characterization and initial biological evaluation of the polymer nanoparticles is proposed in this report and the results presented could guide the future design of amphiphilic polymer NPs for theranostic applications.”

PEG-PLGA from PolySciTech used in development of curcumin-based therapy for ocular cancer treatment

Thursday, September 2, 2021, 9:04 AM ET

Curcumin is a powerful anti-oxidant compound which has properties that prevent tumor metastasis and motion. Although it is present in turmeric, simply eating turmeric (or turmeric powder/prepared foods) will not provide patients with any therapeutically meaningful quantity of curcumin as this compound has very bad water solubility and does not cross over the intestinal tract well. That being said, curcumin provided in a carrier formulation as an injectable or otherwise deliverable compound can aid in cancer treatment. Recently, researchers at University of Rhode Island used PEG-PLGA (AK026) from PolySciTech (www.polyscitech.com) to produce curcumin-loaded nanoparticles. They embedded these in a thermosensitive gel and tested the system for use against uveal melanoma. This treatment holds promise to improve therapies against cancer. Read more: Xie, Lingxiao, Weizhou Yue, Khaled Ibrahim, and Jie Shen. "A Long-Acting Curcumin Nanoparticle/In Situ Hydrogel Composite for the Treatment of Uveal Melanoma." Pharmaceutics 13, no. 9 (2021): 1335. https://www.mdpi.com/1243808

“Uveal melanoma (UM) is the most common primary intraocular tumor in adults with high mortality. In order to improve prognosis and survival of UM patients, it is critical to inhibit tumor progression and metastasis as early as possible after the initial presentation/diagnosis of the disease. Sustained local delivery of antitumor therapeutics in the posterior region can potentially achieve long-term UM inhibition, improve target therapeutic delivery to the posterior segments, as well as reduce injection frequency and hence improved patient compliance. To address the highly unmet medical need in UM therapy, a bioinspired in situ gelling hydrogel system composed of naturally occurring biopolymers collagen and hyaluronic acid was developed in the present research. Curcumin with anti-cancer progression, anti-metastasis effects, and good ocular safety was chosen as the model therapeutic. The developed in situ gelling delivery system gelled at 37 °C within two minutes and demonstrated excellent biocompatibility and slow degradation. The curcumin-loaded nanoparticle/hydrogel composite was able to sustain release payload for up to four weeks. The optimized nanoparticle/hydrogel composite showed effective inhibition of human UM cell proliferation. This novel nanoparticle/in situ hydrogel composite demonstrated a great potential for the treatment of the rare and devastating intraocular cancer. Keywords: in situ hydrogel; nanoparticle/hydrogel composite; sustained delivery; curcumin; uveal melanoma”

PEG-PLGA and PLGA from PolySciTech used in research on nanoparticle fate within the brain

Tuesday, August 31, 2021, 10:13 AM ET

Nanoparticle motion within the brain is a complicated process which is driven by the various chemical factors involved with cellular recognition and disposition towards the particles as well as the particle tendency to aggregate or ability to cross membranes. Recently, researchers from University of Washington used PEG-PLGA (AK106) and PLGA (AP059) to create a series of nanoparticles with varying surfactant-related exteriors. They then fluorescently stained these polymers and carefully tracked their motion through brain tissue to determine their motility and fate. This research holds promise to improve future nanoparticle derived therapies against brain diseases. Read more: Joseph, Andrea, Georges Motchoffo Simo, Torahito Gao, Norah Alhindi, Nuo Xu, Daniel J. Graham, Lara J. Gamble, and Elizabeth Nance. "Surfactants influence polymer nanoparticle fate within the brain." Biomaterials (2021): 121086. https://www.sciencedirect.com/science/article/pii/S0142961221004427

“Abstract: Drug delivery to the brain is limited by poor penetration of pharmaceutical agents across the blood-brain barrier (BBB), within the brain parenchyma, and into specific cells of interest. Nanotechnology can overcome these barriers, but its ability to do so is dependent on nanoparticle physicochemical properties including surface chemistry. Surface chemistry can be determined by a number of factors, including by the presence of stabilizing surfactant molecules introduced during the formulation process. Nanoparticles coated with poloxamer 188 (F68), poloxamer 407 (F127), and polysorbate 80 (P80) have demonstrated uptake in BBB endothelial cells and enhanced accumulation within the brain. However, the impact of surfactants on nanoparticle fate, and specifically on brain extracellular diffusion or intracellular targeting, must be better understood to design nanotherapeutics to efficiently overcome drug delivery barriers in the brain. Here, we evaluated the effect of the biocompatible and commonly used surfactants cholic acid (CHA), F68, F127, P80, and poly(vinyl alcohol) (PVA) on poly(lactic-co-glycolic acid)-poly(ethylene glycol) (PLGA-PEG) nanoparticle transport to and within the brain. The inclusion of these surfactant molecules decreases diffusive ability through brain tissue, reflecting the surfactant's role in encouraging cellular interaction at short length and time scales. After in vivo administration, PLGA-PEG/P80 nanoparticles demonstrated enhanced penetration across the BBB and subsequent internalization within neurons and microglia. Surfactants incorporated into the formulation of PLGA-PEG nanoparticles therefore represent an important design parameter for controlling nanoparticle fate within the brain.”

PLGA-PEG-Mal from PolySciTech used in research on antibody-targeting of nanoparticles

Monday, August 23, 2021, 10:55 AM ET

Use of antibodies for generation of targeted nanoparticles is a popular mechanism used within drug-delivery systems to provide for localization of drug molecules. However, since anitbodies have specific 3-dimensional shapes as a result of the various parameters including folding and orientation of the molecule, the manner in which they are attached plays a role in their performance. Recently, researchers at Sungkyunkwan University and Chung-Ang University (Korea) used PLGA-PEG-Mal (AI053) and PLGA (AP041) from PolySciTech to generate reactive nanoparticles for antibody adhesion testing. This research holds promise to improve development of targeted nanoparticles in the future. Lee, Na Kyeong, Chi-Pin James Wang, Jaesung Lim, Wooram Park, Ho-Keun Kwon, Se-Na Kim, Tae-Hyung Kim, and Chun Gwon Park. "Impact of the conjugation of antibodies to the surfaces of polymer nanoparticles on the immune cell targeting abilities." Nano Convergence 8, no. 1 (2021): 1-11. https://nanoconvergencejournal.springeropen.com/articles/10.1186/s40580-021-00274-7

“Abstract: Antibodies have been widely used to provide targeting ability and to enhance bioactivity owing to their high specificity, availability, and diversity. Recent advances in biotechnology and nanotechnology permit site-specific engineering of antibodies and their conjugation to the surfaces of nanoparticles (NPs) in various orientations through chemical conjugations and physical adhesions. This study proposes the conjugation of poly(lactic-co-glycolic acid) (PLGA) NPs with antibodies by using two distinct methods, followed by a comparison between the cell-targeting efficiencies of both techniques. Full-length antibodies were conjugated to the PLGA-poly(ethylene glycol)-carboxylic acid (PLGA-PEG-COOH) NPs through the conventional carbodiimide coupling reaction, and f(ab′)2 antibody fragments were conjugated to the PLGA-poly(ethylene glycol)-maleimide(PLGA-PEG-Mal) NPs through interactions between the f(ab′)2 fragment thiol groups and the maleimide located on the nanoparticle surface. The results demonstrate that the PLGA nanoparticles conjugated with the f(ab′)2 antibody fragments had a higher targeting efficiency in vitro and in vivo than that of the PLGA nanoparticles conjugated with the full-length antibodies. The results of this study can be built upon to design a delivery technique for drugs through biocompatible nanoparticles.”

Chitosan-fluorescein from PolySciTech used in development of bioadhesive glue for surgical repair

Monday, August 23, 2021, 10:54 AM ET

A valuable tool for use in either surgery or treatment of traumatic injuries is an adhesive which can stick to human tissues and bind them together for a period of time before biodegrading away. Recently, researchers at Massachusetts Institute of Technology used Chitosan-Fluorescein (Kito-8) from PolySciTech (www.polyscitech.com) as part of their development of a glue system for surgical repair applications. This research holds promise to improve wound treatment and tissue repair. Read more: Yuk, Hyunwoo, Jingjing Wu, Tiffany L. Sarrafian, Xinyu Mao, Claudia E. Varela, Ellen T. Roche, Leigh G. Griffiths, Christoph S. Nabzdyk, and Xuanhe Zhao. "Rapid and coagulation-independent haemostatic sealing by a paste inspired by barnacle glue." Nature Biomedical Engineering (2021). https://www.nature.com/articles/s41551-021-00769-y.pdf?origin=ppub

“Abstract: Tissue adhesives do not normally perform well on tissues that are covered with blood or other bodily fluids. Here we report the design, adhesion mechanism and performance of a paste that haemostatically seals tissues in less than 15 s, independently of the blood-coagulation rate. With a design inspired by barnacle glue (which strongly adheres to wet and contaminated surfaces owing to adhesive proteins embedded in a lipid-rich matrix), the paste consists of a blood-repelling hydrophobic oil matrix containing embedded microparticles that covalently crosslink with tissue surfaces on the application of gentle pressure. It slowly resorbs over weeks, sustains large pressures (approximately 350 mm Hg of burst pressure in a sealed porcine aorta), makes tough (interfacial toughness of 150–300 J m−2) and strong (shear and tensile strengths of, respectively, 40–70 kPa and 30–50 kPa) interfaces with blood-covered tissues, and outperforms commercial haemostatic agents in the sealing of bleeding porcine aortas ex vivo and of bleeding heart and liver tissues in live rats and pigs. The paste may aid the treatment of severe bleeding, even in individuals with coagulopathies.”

PEG-PLGA from PolySciTech used in development of macitentan particles to prime tumors for immunotherapy

Tuesday, August 17, 2021, 10:12 AM ET

Immunotherapy holds great promise to provide for treatments against cancers by relying on the human immune system to target and destroy the cancer cells. Unfortunately, tumors have a wide array of protecting themselves from immune system which must be overcome in order for immunotherapy to be effective. Recently, researchers at Sungkyunkwan University, National Marine Biodiversity Institute of Korea, and Korea Research Institute of Bioscience & Biotechnology used mPEG-PLGA (AK037) from PolySciTech (www.polyscitech.com) to create polymeric micelle nanoparticles containing macitentan which reduces the ability for the tumor to suppress immune response. This research holds promise to improve the application of immunotherapy. Read more: Son, Soyoung, Jung Min Shin, Sol Shin, Chan Ho Kim, Jae Ah Lee, Hyewon Ko, Eun Sook Lee, Jae Min Jung, Jeongyun Kim, and Jae Hyung Park. "Repurposing macitentan with nanoparticle modulates tumor microenvironment to potentiate immune checkpoint blockade." Biomaterials (2021): 121058. https://www.sciencedirect.com/science/article/pii/S0142961221004142

“Abstract: Immune checkpoint therapy (ICT), which reinvigorates cytotoxic T cells, provides clinical benefits as an alternative to conventional cancer therapies. However, its clinical response rate is too low to treat an immune-excluded tumor, owing to the presence of abundant stromal elements impeding the penetration of immune cells. Here, we report that macitentan, a dual endothelin receptor antagonist approved by the FDA to treat pulmonary arterial hypertension, can be repositioned to modulate the desmoplastic tumor microenvironment (TME). In the 4T1 orthotopic tumor model, the polymeric nanoparticles bearing macitentan (M-NPs) prevent fibrotic progression by regulating the function of cancer-associated fibroblasts, attenuate the biogenesis of cancer cell-derived exosomes, and modulate the T cell subsets and distribution in TME. These results demonstrate that the M-NPs effectively reorganize the immunosuppressive TME by targeting the endothelin-1 axis and consequently exhibit synergistic antitumor effects in combination with ICT.”

mPEG-PLA and PLA from PolySciTech used in development of novel block copolymers for nanoparticle formulations

Tuesday, August 10, 2021, 11:50 AM ET

In most situations PEGylated particles provide for highly-safe mechanisms to improve flow and residence time of particles in the human body. In specific instances, however, certain people will develop an immune reaction to PEG itself which limits the usefulness of these particles. Recently, researchers at Universita degli Studi di Salerno (University of Salerno, Fiscaiano, Italy) used PLA (AP005, AP079) and mPEG-PLA (AK009) from PolySciTech (www.polyscitech.com) to create nanoparticles with PEGylated exteriors as well as particles with a nove inulin coating. This research indicates that inulin can be used as an alternative to PEG for use in people who have experienced allergic reactions to PEG. Read more: Sardo, Carla, Teresa Mencherini, Carmela Tommasino, Tiziana Esposito, Paola Russo, Pasquale Del Gaudio, and Rita Patrizia Aquino. "Inulin-g-poly-D, L-lactide, a Sustainable Amphiphilic Copolymer for Nano-Therapeutics." (2021). https://www.researchsquare.com/article/rs-703619/latest.pdf

“Cancer therapies started to take a big advantage from new nanomedicines on the market. Since then, research tried to better understand how to maximize efficacy whilst maintaining a high safety profile. Polyethylene glycol (PEG), the gold standard for nanomedicines coating design, although in many cases is a winning choice to ensure a long circulation and colloidal stability, in other cases cause, after the first administration, the development in patients of PEG directed immunoglobulins. The phenomenon, called ABC effect, has been studied and correlated with clinical failure because of the premature removal from the circulation by immune mechanism. Therefore, alternatives to PEG need to be found. Here, looking at the backbone structural analogy, the hydrophilicity, flexibility and its GRAS status, the natural polysaccharide Inulin (INU) was investigated as PEG alternative. In particular, the first family of Inulin-gpoly-D,L-lactide amphiphilic copolymers (INU-PLAs) was synthesized. The new materials were fully characterized from the physic-chemical point of view (solubility, 1D and 2D NMR, FT-IR, UV-Vis, GPC, DSC) and showed interesting hybrid properties compared to precursors. Moreover, their ability in forming stable colloids and to serve as a carrier for doxorubicin were investigated and compared with the already well known and well characterized PEGylated counterpart, polyethylene glycol-g-poly-D,L-lactide (PEG-PLA). This preliminary investigation showed INU-PLA to be able to assemble in nanostructures less than 200 nm in size and capable of loading doxorubicin with an encapsulation efficiency in the same order of magnitude of PEG-PLA analogues. Keywords: Inulin, PLA, PEG alternative, nanoparticles, doxorubicin”

PLCL Morphological Form based on LA:CL ratio

Monday, August 9, 2021, 10:19 AM ET

Poly(lactide-co-caprolactone) has a varying degree to glass and melt transitions depending on the LA:CL ratio. In general, the closer the LA:CL ratio is to either end (primarily LA or primarily CL) then crystallinity is enabled for chain-to-chain attraction. When the LA:CL is close to 50:50 mix between the two components then the product has a very low glass transition and melt point with little chain-to-chain interaction. Additionally, the use of more crystalline L-enantiomer lactide improves mechanical durability as well. The morphology (at room temperature) of several of Akina's Products demonstrates this:

Morphology at room temperature (RT):

AP151: PLCL LA:CL 70:30 acid endcap (Mn 75,000-85,000 Da) DL-enantiomer
--> pale straw-colored translucent polymer. Rubbery texture at RT.

AP260: PLLCL LA:CL 90:10 acid endcap (Mn 100,000-200,000 Da) (L-enantiomer)
--> opaque, fluffy, white at RT. Feels dry to the touch.

AP263: PLCL LA:CL 80:20 acid endcap (Mn 75,000-85,000 Da) DL-enantiomer
--> translucent white at room temp. Rubbery texture.

Akina Scientific Posters from 2021 Controlled Release Society now available in full-content pdf

Thursday, August 5, 2021, 10:18 AM ET

As part of work with the Food and Drug Administration (FDA), Akina, Inc. has performed many experiments relating to development work in characterization methods for poly(lactide-co-glycolide) (PLGA). At the 2021 Controlled Release Society annual meeting scientific posters were presented relating to these experiments and their results. Akina, Inc. provides contracted analysis and research for outside customers through the Akinalytics (http://www.akinalytics.com/) department. You can see these and other publications from Akina, Inc. at our listing here (http://polyscitech.com/currentResearch/publications.php)

J. Garner, J. Hadar, S. Skidmore, F. Jessmon, H. Park, K. Park, Y. K. Jhon, B. Qin, Y. Wang. “Scanning Analysis of Semi-Solvent Impact (SASSI) assays of naltrexone microparticles manufactured using different solvents” Scientific Poster presented at 2021 annual meeting of Controlled Release Society

J. Garner, J. Hadar, S. Skidmore, F. Jessmon, H. Park, K. Park, Y. K. Jhon, B. Qin, Y. Wang. “Effect of Solvent Isomeric Structures on the Dissolution of PLGAs with Different Lactide:Glycolide (L:G) Ratios” Scientific Poster presented at 2021 annual meeting of Controlled Release Society

J. Garner, J. Hadar, S. Skidmore, F. Jessmon, H. Park, K. Park, Y. K. Jhon, B. Qin, Y. Wang. “Effect of Solvent Isomeric Structures on the Dissolution of PLGAs with Different Lactide:Glycolide (L:G) Ratios” Scientific Poster presented at 2021 annual meeting of Controlled Release Society

Gene delivery potential of PLA-PEG-Mal points to potential to use block polymers for mRNA vaccines

Tuesday, July 27, 2021, 12:08 PM ET

Current strategies primarily use lipid nanoparticles and liposomes for delivery of mRNA for vaccines such as the Pfizer and Moderna vaccines against Covid. The potential for delivery of genetic material has proven itself to be a powerful tool. Recent research has indicated the potential for gene delivery by PLA-PEG-Mal type polymeric particles as a potential therapy for irritable bowel disease. This points to the potential to use this class of polymers for delivery of mRNA and other genes as part of vaccination and other applications. Find these and other polymers at www.polyscitech.com

Verma, Priyanka, Aasheesh Srivastava, Chittur V. Srikanth, and Avinash Bajaj. "Nanoparticle-mediated gene therapy strategies for mitigating inflammatory bowel disease." Biomaterials science 9, no. 5 (2021): 1481-1502.https://pubs.rsc.org/en/content/articlehtml/2020/bm/d0bm01359e


Abstract: Inflammatory bowel disease (IBD) is an autoimmune disorder of the gastrointestinal tract (GIT) where Ulcerative Colitis (UC) displays localized inflammation in the colon, and Crohn's Disease (CD) affects the entire GIT. Failure of current therapies and associated side-effects bring forth serious social, economic, and health challenges. The gut epithelium provides the best target for gene therapy delivery vehicles to combat IBD. Gene therapy involving the use of nucleic acid (NA) therapeutics faces major challenges due to the hydrophilic, negative-charge, and degradable nature of NAs. Recent success in the engineering of biomaterials for gene therapy and their emergence in clinical trials for various diseases is an inspiration for scientists to develop gene therapy vehicles that can be easily targeted to the desired tissues for IBD. Advances in nanotechnology have enabled the formulations of numerous nanoparticles for NA delivery to mitigate IBD that still faces challenges of stability in the GIT, poor therapeutic efficacy, and targetability. This review presents the challenges of gene therapeutics, gastrointestinal barriers, and recent advances in the engineering of nanoparticles for IBD treatment along with future directions for successful translation of nanoparticle-mediated gene therapeutics in clinics.

Nuplon Heat-Curable Resin Free Samples Available For Testing and Applications Research

Tuesday, July 27, 2021, 11:37 AM ET

In an effort to aid in combating plastic contamination of waterways and landfills, Akina, Inc. has recently developed a biodegradable, self-crosslinking resin. Intellectual property protection on the background technology for Nuplon was filed by Akina, Inc. with a priority date of June 25, 2020 and patent protection is currently pending under filing number US 2021070743. Akina, Inc. is actively seeking a partner interested in end-product applications for the Nuplon material. To that end, we’re putting Nuplon in the hands of the smartest people we know.


Starting from July, 2021, samples of “pour-and-cure” heat-curable Nuplon resin are free to request from the website (https://akinainc.com/polyscitech/products/NuPlon/index.php) with only cost being shipping charges for USPS shipping. Additionally, on any order simply type “Nuplon” into the “Special Instructions” section to receive your free sample.

-Nuplon Details-

Description: Prepolymer is a set of low molecular weight oligomeric esters comprised of varying lengths of lactides and other esters combined with multifunctional alcohols and multifunctional acids. Prepolymer is a viscous liquid (Brookfield spindle, 20 ⁰C, 1000 – 3000 cP). To cure: Pour solution into desired shape of mold or onto components. Nuplon has proven to be strongly adhesive so use of either PTFE, silicone rubber, or molds coated with mold-release aid is suggested to prevent adhesion. Heat in an oven at 150 – 170 ⁰C overnight (16-24 hours) to cure. Afterwards, demold product and cut/machine to form the final shape. Adhesion: Nuplon prepolymer has strong adhesive properties and may be used to attach two components together. For this simply clamp the pieces together with the Nuplon between them and cure as described above. Post-Cure Performance: Final product is optically clear, hard plastic. Mechanical: Elastic Modulus (0.1 – 1% strain): 4.8 + 1.6 MPa, Tensile Strength: 31.0 + 19.2 MPa, Extensibility: 5.3 + 1.6 % strain, Temperature stable up to 350 ⁰C when dry. Degradation: Under normal exposure to humidity in an indoor location (20 – 25C, 30 - 80% RH) product softens after about six months and degrades after about 1-2 years forming into a soft, gel. When hydrated, will quickly become flexible after a day or two and fully degrade to non-toxic products after 2-3 months in water. For other applications and technical information visit http://www.nuplon.com/tech

PLGA from PolySciTech used in development of probiotic intestinal delivery

Tuesday, July 27, 2021, 11:37 AM ET

Humans require certain forms of bacteria in their intestine in order to provide for digestion as well as prevention of the growth of pathological bacterial. Despite the plethora of consumer products advertising probiotic contents these, in general, are poorly effective at establishing probiotic colonies in the intestines due to acidic degradation in the stomach. Recently, researchers at Pusan National University, The University of Arizona, Pohang University of Science and Technology, and Korea University used PLGA (AP121) from PolySciTech (www.polyscitech.com) as part of development of a delivery system for probiotics. This holds promise to assist people who have digestive disorders. Read more: Kim, Jihyun, Shwe Phyu Hlaing, Juho Lee, Aruzhan Saparbayeva, Sangsik Kim, Dong Soo Hwang, Eun Hee Lee et al. "Exfoliated bentonite/alginate nanocomposite hydrogel enhances intestinal delivery of probiotics by resistance to gastric pH and on-demand disintegration." Carbohydrate Polymers (2021): 118462. https://www.sciencedirect.com/science/article/pii/S0144861721008493 “Highlights: LGG was encapsulated in exfoliated bentonite/alginate nanocomposite hydrogels. Improved hydrogel pore size dramatically enhanced LGG survival at gastric pH. Complete intestinal release of LGG was observed after hydrogel disintegration. Fecal recovery of bentonite/alginate LGG was 6-fold greater than of alginate LGG. Abstract: In this study, we developed Lactobacillus rhamnosus GG (LGG)-encapsulating exfoliated bentonite/alginate nanocomposite hydrogels for protecting probiotics by delaying gastric fluid penetration into the nanocomposite and their on-demand release in the intestine. The pore size of the bentonite/alginate nanocomposite hydrogels (BA15) was two-fold smaller than that of alginate hydrogel (BA00). Following gastric pH challenge, the survival of LGG in BA15 decreased by only 1.43 log CFU/g as compared to the 6.25 log CFU/g decrease in alginate (BA00). Further, the internal pH of BA15 decreased more gradually than that of BA00. After oral administration in mice, BA15 maintained shape integrity during gastric passage, followed by appropriate disintegration within the target intestinal area. Additionally, a fecal recovery experiment in mice showed that the viable counts of LGG in BA15 were six-fold higher than those in BA00. The findings suggest the exfoliated bentonite/alginate nanocomposite hydrogel as a promising platform for intestinal delivery of probiotics. Keywords: probiotics alginate bentonite nanocomposite gastric pH resistance intestinal delivery”

PLGA-PEG-Maleimide from PolySciTech used in the development of gefitinib loaded/p28 targeted nanoparticles for lung cancer treatment

Tuesday, July 27, 2021, 11:36 AM ET

Delivery of medicinal molecules to cancer cells is difficult based on the ability of the medicine to specifically target towards the tumor site as well as to cross into the cancer cell. This can be improved by attaching targeting ligands to the nanoparticles to improve their uptake. Recently, researchers at University of Lisbon, University of Porto, and CESPU-Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde used PLGA-PEG-Mal (AI110) from PolySciTech (www.polyscitech.com) to develop targeted nanoparticles for delivery of gefitinib to lung cancer. This research holds promise to improve treatment options for this fatal disease. Read more: Garizo, Ana Rita, Flávia Castro, Cláudia Martins, Andreia Almeida, Tiago P. Dias, Fábio Fernardes, Cristina C. Barrias, Nuno Bernardes, Arsénio M. Fialho, and Bruno Sarmento. "p28-functionalized PLGA nanoparticles loaded with gefitinib reduce tumor burden and metastases formation on lung cancer." Journal of Controlled Release (2021). https://www.sciencedirect.com/science/article/pii/S0168365921003783

“Abstract: Lung cancer is still the main cause of cancer-related deaths worldwide. Its treatment generally includes surgical resection, immunotherapy, radiotherapy, and chemo-targeted therapies such as the application of tyrosine kinase inhibitors. Gefitinib (GEF) is one of them, but its poor solubility in gastric fluids weakens its bioavailability and therapeutic activity. In addition, like all other chemotherapy treatments, GEF administration can cause damage to healthy tissues. Therefore, the development of novel GEF delivery systems to increase its bioavailability and distribution in tumor site is highly demanded. Herein, an innovative strategy for GEF delivery, by functionalizing PLGA nanoparticles with p28 (p28-NPs), a cell-penetrating peptide derived from the bacterial protein azurin, was developed. Our data indicated that p28 potentiates the selective interaction of these nanosystems with A549 lung cancer cells (active targeting). Further p28-NPs delivering GEF (p28-NPs-GEF) were able to selectively reduce the metabolic activity of A549 cells, while no impact was observed in non-tumor cells (16HBE14o-). In vivo studies using A549 subcutaneous xenograft showed that p28-NPs-GEF reduced A549 primary tumor burden and lung metastases formation. Overall, the design of a p28-functionalized delivery nanosystem to effectively penetrate the membranes of cancer cells while deliver GEF could provide a new strategy to improve lung cancer therapy. Keywords Azurin Cell penetrating peptide EGFR inhibitor Nanosized drug delivery system Active targeting Cancer therapy”

These posts are syndicated from John Garner's blog at http://jgakinainc.blogspot.com/ where you can post a question or comment. (Load took 0.29456782341003 seconds)


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