Monthly Archives: May 2017

PolySciTech Thermogelling PLGA-PEG-PLGA used in development of cataract therapy to prevent blindness

Cataract surgery is typically successful in returning sight to people who have suffered from loss of sight due to cloudiness of the eye’s lense. One complication from the surgery, however, is the formation of Posterior capsule opacity, which once again removes vision by making it impossible to see through the affected portions of the eye. Recently, researchers at The Ohio State University utilized PLGA-PEG-PLGA from PolySciTech (www.polyscitech.com) (PolyVivo AK024) to develop a thermogel-based delivery system for cyclosporine A to prevent PCO. This research holds promise to restore sight to people affected by this condition. Read more: Gervais, Kristen J. “Evaluation of a biodegradable thermogel polymer for intraocular delivery of cyclosporine A to prevent posterior capsule opacification.” PhD diss., The Ohio State University, 2017. (https://etd.ohiolink.edu/pg_10?0::NO:10:P10_ACCESSION_NUM:osu1492101014927609, https://etd.ohiolink.edu/!etd.send_file?accession=osu1492101014927609&disposition=inline)

“Abstract: Purpose: To utilize a thermosensitive hydrogel (thermogel) polymer to achieve sustained release of cyclosporine A (CsA) for targeted destruction of lens epithelial cells (LEC) and reduction of posterior capsule opacification (PCO) after cataract surgery. Part I of the study evaluated the drug delivery system in an ex vivo canine model of PCO, while Part II evaluated intraocular delivery in an in vivo rabbit model. Methods. A PLGA-PEG-PLGA thermogel polymer was formulated to release CsA ([300µg/mL]) or vehicle (ethanol). PART I: Extracapsular cataract extraction and intraocular lens (IOL) placement were performed in 24 canine cadaver globes. Lens capsule explants with residual LEC were treated with 200µL of CsA-eluting (n=12) or vehicle-eluting (n=12) thermogel and maintained in culture. Posterior capsule coverage by LEC was graded following 7 (n=8), 14 (n=6), or 28 (n=10) days of treatment. Following histology, LEC were manually quantified via light microscopy from capsules treated for 28-days. CsA concentration in culture media was quantified by tandem liquid chromatography-mass spectrometry (LC-MS/MS) at each time point. Differences in percent posterior capsule coverage and LEC counts were analyzed by the student’s t-test with Welch’s correction. PART II: Phacoemulsification cataract surgery and IOL placement were performed in 10 adult rabbits (20 eyes). Ten left eyes served as negative controls and were treated with viscoelastic material only. Five right eyes were treated with 200µL CsA-eluting thermogel polymer, and five right eyes were treated with vehicle-eluting thermogel polymer. Clinical ophthalmic examination parameters and PCO grading were performed daily for 6 days post-operatively, and then weekly until the termination of the study at 49 days. Aqueous humor samples were analyzed for CsA concentration at day 6 post-operatively. Following euthanasia, globes were collected and analyzed histologically for degree of PCO formation and any evidence of ocular toxicity. Clinical examination parameters were compared between treatment groups using the Wilcoxon signed rank or Wilcoxon rank sum test. Results. PART I: Posterior capsule coverage by LEC was significantly reduced in CsA-thermogel treated capsules compared to vehicle-treated capsules. Histologic LEC counts were significantly lower in CsA-thermogel treated capsules. Cumulative CsA release from the thermogel was greater than 10µg/mL over a minimum of 7 days. PART II: No significant differences in clinical PCO scores were identified when comparing treatment with CsA-eluting thermogel to vehicle-eluting thermogel. The rate of onset and severity of PCO formation were significantly decreased in thermogel-treated eyes (CsA- and thermogel-treated data combined) compared to non-thermogel-treated eyes up to 4 weeks post-operatively. At the conclusion of the study, no significant differences in PCO formation were found clinically or histologically between treatment groups. The mean aqueous humor CsA level at day 6 post-operatively was 3.2pg/mL. No direct toxic effects of the thermogel polymer or CsA were documented in any eyes. Conclusions. Use of a CsA-eluting thermogel polymer may be a viable pharmacologic method for inducing targeted LEC death and reducing PCO formation. Intraocular administration of the drug delivery system is feasible and does not result in ocular toxicity.”

PolySciTech PS-PLA and PLA used in development of protein-loaded nanoparticles to study polymer-protein interactions

Proteins are a class of biopolymers which serve a multitude of critical functions within living organisms. Some proteins, such as collagen and keratin, provide mechanical support while others act as enzymes performing critical processes such as cellular metabolism, signaling, membrane transport. Because of their many biochemical interactions, protein-based medicines hold great promise for treating a wide range of diseases. Proteins are long biopolymers that are folded into a specific 3D orientation by a series of intramolecular forces, some of which are more delicate than others. The exact shape of the fold is critical to how the protein functions and if the protein is unfolded it, typically, can never be folded back into the same shape it was again. A simple, everyday example of this is cooking an egg. As an egg is heated, the proteins in the egg transition from folded into linear forms and link onto one another aggregating into insoluble crosslinked gels. In this way, the proteins transition from the clear, viscous fluid of a freshly cracked egg into the white solid gel associated with a well cooked egg. Similarly, many industrial and laboratory practices such as processing with organic solvents, high temperatures, etc. can cause denaturation rendering the protein useless. This, in addition to the high water-solubility of proteins, makes generating controlled-delivery systems for them particularly challenging. Recently, researchers from University of Washington utilized PolySciTech (www.polyscitech.com) PS-PLA (PolyVivo AK042) and Polylactide to make nanoparticles loaded with albumin to study the interaction between polymers and proteins for drug-delivery applications. This research holds promise for enabling the development of a wide array of controlled-delivery systems of protein-based drugs. Read more: Smith, Josh, Kayla G. Sprenger, Rick Liao, Andrea Joseph, Elizabeth Nance, and Jim Pfaendtner. “Determining dominant driving forces affecting controlled protein release from polymeric nanoparticles.” Biointerphases 12, no. 2 (2017): 02D412. http://avs.scitation.org/doi/abs/10.1116/1.4983154

“ABSTRACT: Enzymes play a critical role in many applications in biology and medicine as potential therapeutics. One specific area of interest is enzyme encapsulation in polymer nanostructures, which have applications in drug delivery and catalysis. A detailed understanding of the mechanisms governing protein/polymer interactions is crucial for optimizing the performance of these complex systems for different applications. Using a combined computational and experimental approach, this study aims to quantify the relative importance of molecular and mesoscale driving forces to protein release from polymeric nanoparticles. Classical molecular dynamics (MD) simulations have been performed on bovine serum albumin (BSA) in aqueous solutions with oligomeric surrogates of poly(lactic-co-glycolic acid) copolymer, poly(styrene)-poly(lactic acid) copolymer, and poly(lactic acid). The simulated strength and location of polymer surrogate binding to the surface of BSA have been compared to experimental BSA release rates from nanoparticles formulated with these same polymers. Results indicate that the self-interaction tendencies of the polymer surrogates and other macroscale properties may play governing roles in protein release. Additional MD simulations of BSA in solution with poly(styrene)-acrylate copolymer reveal the possibility of enhanced control over the enzyme encapsulation process by tuning polymer self-interaction. Last, the authors find consistent protein surface binding preferences across simulations performed with polymer surrogates of varying lengths, demonstrating that protein/polymer interactions can be understood in part by studying the interactions and affinity of proteins with small polymer surrogates in solution.”

PolySciTech polyesters used in development of neuroprotective controlled-delivery system for glaucoma treatment

Glaucoma, a disease in which damage to the optic nerve leads to eventual blindness, involves oxidative stress that leads to extensive optic nerve injury. Preventing oxidative stress (e.g. reducing reactive oxygen species formation with the cells) is an effective means to prevent cellular death and delay nerve damage. It has been found that reducing agents (such as phenylphosphine-borane complexes) can act to prevent the over-formation of reactive oxygen species and reduce nerve damage from Glaucoma. Administering these medicines over the course of this chronic disease, however, requires repeat injections in the same ocular location, which is inconvenient to both patient and provider. A better strategy is to deliver a single injection every few months which delivers the neuroprotective agent in a controlled manner. Recently, researchers working at University of Wisconsin and McGill University (Canada) utilized many degradable polyesters (PLGA, PLA, PLCL, PDOCL) from PolySciTech (www.polyscitech.com) (PolyVivo cat# AP001, AP002, AP003, AP004, AP006, AP007, AP008, AP010, AP011, AP013, AP014, AP016, AP017, AP018, AP020, AP021, AP023, AP024, AP030, AP031, AP032, and AP034) to develop such a controlled delivery system. This research holds promise for improved glaucoma therapy to delay the progression of this disease. Read more: Janus, David A., Christopher J. Lieven, Megan E. Crowe, and Leonard A. Levin. “Polyester-Based Microdisc Systems for Sustained Release of Neuroprotective Phosphine-Borane Complexes.” Pharmaceutical Development and Technology just-accepted (2017): 1-32. http://www.tandfonline.com/doi/abs/10.1080/10837450.2017.1333516

“Abstract: Phosphine-borane complexes are recently developed redox-active drugs that are neuroprotective in models of optic nerve injury and radioprotective in endothelial cells. However, a single dose of these compounds is short-lived, necessitating development of sustained-release formulations of these novel molecules. We screened a library of biodegradable co- and non-block polyester polymer systems for release of incorporated phosphine-borane complexes to evaluate them as drug delivery systems for use in chronic disease. Bis(3-propionic acid methyl ester)phenylphosphine borane complex (PB1) was combined with biodegradable polymers based on poly(D,L-lactide) (PDLLA), poly(L-lactide) (PLLA), poly(caprolactone) (PCL), poly(lactide-co-glycide) (PLGA), or poly(dioxanone-co-caprolactone) (PDOCL) to make polymer microdiscs, and release over time quantified. Of 22 polymer-PB1 formulations tested, 17 formed rigid polymers. Rates of release differed significantly based on the chemical structure of the polymer. PB1 released from PLGA microdiscs released most slowly, with the most linear release in polymers of 60:40 LA:GA, acid endcap, Mn 15,000-25,000 and 75:25 LA:GA, acid endcap, Mn 45,000-55,000. Biodegradable polymer systems can therefore be used to produce sustained-release formulations for redox-active phosphine-borane complexes, with PLGA-based systems most suitable for very slow release. Sustained release could enable translation to a clinical neuroprotective strategy for chronic diseases such as glaucoma. Keywords: Phosphine-Borane, Sustained Release, Polymer, Polyester, Neuroprotection”

Movie for using polymer micelles to assist drug dissolution

PolySciTech (www.polyscitech.com) Polymer University: Micelles 103 Movie now posted. Fun and educational look at solubility problems in medicine as well as how block polymers assist with delivery of poorly soluble drugs. Introduces hydrophobicity, hydrophilicity, interfacial tension, and micelle formation in a light-hearted and easy to follow format. https://youtu.be/nd1WOiwsa00

Nanoparticles for oral delivery of insulin developed using PolySciTech mPEG-PLGA

Insulin injections are an effective treatment for diabetes, but are painful and difficult to sustain on a constant basis. Insulin cannot, under normal conditions, be ingested for example as a tablet because the protein is very delicate and will be destroyed by stomach enzymes. Loading of proteins into nanoparticles is not a trivial task as many of the solvents used to process nanoparticles would damage proteins causing them to unfold and denature irreversibly. Recently, researchers working jointly at Massachuesettes Institute of Technology (MIT), CHU de Quebec Research Center (Canada), Harvard Medical School, King Abdulaziz University (Saudi Arabia), and Soonchunhyang University (Korea) utilized mPEG-PLGA from PolySciTech (www.polyscitech.com) (PolyVivo Cat# AK010) to generate insulin loaded nanoparticles by a zinc precipitation technique. This research holds promise not only to provide for improved insulin therapy with greater patient convenience but also to allow for the loading of other proteins into nanoparticles for therapeutic applications. This work was featured both in a research publication and in a PhD Dissertation. Read more: Chopra, Sunandini, Nicolas Bertrand, Jong-Min Lim, Amy Wang, Omid C. Farokhzad, and Rohit Karnik. “Design of Insulin-Loaded Nanoparticles Enabled by Multistep Control of Nanoprecipitation and Zinc Chelation.” ACS Applied Materials & Interfaces 9, no. 13 (2017): 11440-11450. http://pubs.acs.org/doi/abs/10.1021/acsami.6b16854, Dissertation: Chopra, Sunandini. “Development of nanoparticles for oral delivery of insulin.” PhD diss., Massachusetts Institute of Technology, 2017. https://dspace.mit.edu/bitstream/handle/1721.1/108946/986242657-MIT.pdf?sequence=1

“Abstract: Nanoparticle (NP) carriers provide new opportunities for controlled delivery of drugs, and have potential to address challenges such as effective oral delivery of insulin. However, due to the difficulty of efficiently loading insulin and other proteins inside polymeric NPs, their use has been mostly restricted to the encapsulation of small molecules. To better understand the processes involved in encapsulation of proteins in NPs, we study how buffer conditions, ionic chelation, and preparation methods influence insulin loading in poly(lactic-co-glycolic acid)-b-poly(ethylene glycol) (PLGA–PEG) NPs. We report that, although insulin is weakly bound and easily released from the NPs in the presence of buffer ions, insulin loading can be increased by over 10-fold with the use of chelating zinc ions and by the optimization of the pH during nanoprecipitation. We further provide ways of changing synthesis parameters to control NP size while maintaining high insulin loading. These results provide a simple method to enhance insulin loading of PLGA–PEG NPs and provide insights that may extend to other protein drug delivery systems that are subject to limited loading. Keywords: biologics; diabetes; insulin; nanomedicine; oral drug delivery; PLGA−PEG nanoparticles; zinc”

PLGA from PolySciTech used in development of veterinary peptide/nanoparticle-based vaccine against bovine paratuberculosis

In addition to human medical applications, there are also a wide range of veterinary applications for biodegradable polymers. Paratuberculosis is a costly disease of the bovine small intestine which occurs with high prevalence in US dairy herds. Currently available vaccines do not provide complete protection from infection due to poor immune activation. Attenuated virus vaccines against Paratuberculosis can only be used in sheep as they cause cross-reactivity in cattle. For this reason, dairy farmers have relatively little recourse against this disease to protect their herds. Recently, researchers working jointly at Washington State University, the US department of agriculture, and Alexandria University (Egypt) used PLGA from PolySciTech (www.polyscitech.com) (PolyVivo AP054) to create peptide-based vaccine (rather than killed or attenuated-virus) loaded nanoparticles for improved effectiveness. This research holds promise to improve dairy cattle disease resistance which will ensure a more sustainable food supply. Read more: Souza, Cleverson D., John P. Bannantine, Wendy C. Brown, M. Grant Norton, William C. Davis, Julianne K. Hwang, Parissa Ziaei et al. “A nano particle vector comprised of poly lactic‐co‐glycolic acid and monophosphoryl lipid A and recombinant Mycobacterium avium subsp paratuberculosis peptides stimulate a pro‐immune profile in bovine macrophages.” Journal of Applied Microbiology (2017). http://onlinelibrary.wiley.com/doi/10.1111/jam.13491/full

“Abstract: Aims: We evaluated the potential of a nanoparticle (NP) delivery system to improve methods of delivery of candidate peptide based vaccines for Paratuberculosis in cattle. Methods and Results: Peptides derived from Mycobacterium avium subsp paratuberculosis (Map), and the proinflammatory monophosphoryl lipid A (MPLA) were incorporated in polymeric NPs based on poly (D, L-lactide-co-glycolide) (PLGA). The PLGA/MPLA NPs carriers were incubated with macrophages to examine their effects on survival and function. PLGA/MPLA NPs, with and without Map antigens, are efficiently phagocytized by macrophages with no evidence of toxicity. PLGA/MPLA NP formulations did not alter the level of expression of MHC I or II molecules. Expression of TNFα and IL12p40 was increased in Map loaded NPs. T cell proliferation studies using a model peptide from Anaplasma marginale demonstrated that a CD4 T cell recall response could be elicited with macrophages pulsed with the peptide encapsulated in the PLGA/MPLA NP. Conclusions: These findings indicate PLGA/MPLA NPs can be used as a vehicle for delivery and testing of candidate peptide based vaccines. Keywords: PLGA ; monophosphoryl lipid A; Mycobacterium avium subsp. paratuberculosis; Anaplasma marginale ; peptide vaccine”

Biodegradable polyesters (PLGA, PLA, PCL) from PolySciTech investigated for controlling Mg-based cardiovascular stent degradation

One treatment for cardiovascular disease is balloon angioplasty, in which a stent is emplaced at the site of arterial blockage in the heart. Initial work with bare-metal stents had reasonably successful results in keeping the artery open by providing structural support but, over time, the tissue of the vessel would grow back over the stent and into the interior portion of it reclosing the artery by a process known as restenosis. A variety of strategies have been applied to solving this issue. One strategy is to utilize a temporary, biodegradable stent comprised primarily of magnesium, which slowly corrodes back into biocompatible magnesium ions leaving no foreign surface for the arterial cells to grow over. However, the speed of Mg breakdown, on its own, is too rapid for stent application. Recently, researchers working at University of California at Riverside and Norco College utilized PLGA, PLLA, and PCL from PolySciTech (www.polyscitech.com) PLLA (No. AP007), PLGA (90:10) (No. AP049), PLGA (50:50) (No. AP089), and PCL (No. AP009) to develop a series of biodegradable coatings to cover over magnesium-type stents. These coatings were used to delay Mg degradation and to improve the stent-surface interaction with arterial cells. This research holds promise for improved cardiovascular treatment by using biodegradable stents which do not suffer from late-stage restenosis. Read more: Jiang, Wensen, Qiaomu Tian, Tiffany Vuong, Matthew Shashaty, Chris Gopez, Tian Sanders, and Huinan Liu. “Comparison Study on Four Biodegradable Polymer Coatings for Controlling Magnesium Degradation and Human Endothelial Cell Adhesion and Spreading.” ACS Biomaterials Science & Engineering (2017). http://pubs.acs.org/doi/abs/10.1021/acsbiomaterials.7b00215

“Magnesium (Mg)-based bioresorbable cardiovascular scaffold (BCS) is a promising alternative to conventional permanent cardiovascular stents, but it faces the challenges of rapid degradation and poor endothelium recovery after device degradation. To address these challenges, we investigated poly(l-lactic acid) (PLLA), poly(lactic-co-glycolic acid) (PLGA) (90:10), PLGA (50:50), and polycaprolactone (PCL) coatings on Mg, respectively, and evaluated their surface and biological properties. Intact polymer coatings with complete coverage on Mg substrate were achieved. The biological performance of the materials was evaluated by culturing with human umbilical vein endothelial cells (HUVECs) in vitro using the direct culture method. The pH of the culture media and Mg2+ and Ca2+ ion concentrations in the media were measured after culture to characterize the degradation rate of the materials in vitro. The results showed that the PLGA (50:50) coating improved the adhesion and spreading of HUVECs the most among the four polymer coatings. Moreover, we found three possible factors that promoted HUVECs directly attached on the surface of PLGA (50:50)-coated Mg: (1) the higher concentration of Mg2+ ions released into culture media with a concentration range of 9–15 mM; (2) the lower Ca2+ ion concentration in culture media at 1.3–1.6 mM; and (3) the favorable surface conditions of PLGA (50:50), when compared with the other sample groups. This in vitro study provided the first evidence that the PLGA (50:50) is a promising coating material for Mg-based biodegradable metals toward potential cardiovascular or neurovascular applications. Keywords: bioresorbable cardiovascular scaffold; bioresorbable magnesium implants; human umbilical vein endothelial cells; in vitro direct culture method; polymer coatings”

PLGA-PEG-amine from PolySciTech used to generate brain-penetrating nanoparticles for treatment of neural diseases

A significant problem in treating disease which affect the brain is that getting medicine into the brain tissue is very difficult. This is due to the ‘blood-brain-barrier’ which prevents medicines in the bloodstream from crossing over into the brain tissue. This is a unique feature of the brain, as other organs (kidneys, liver, lungs, etc.) readily absorb medicines from the blood stream. A simple method to overcome this barrier is to simply dose the medicine so high that even if a small portion of the drug crosses into the brain it is effective. However, this strategy does not work with medicines that have side-effects at high doses. Another method of dealing with this problem is to generate medicine-loaded nanoparticles which are specifically modified in such a way as to allow them to penetrate across the blood-brain barrier so they can deliver medicine into the brain for treatment of neural diseases. Recently, researchers working jointly at University of Southern Denmark (Denmark) and Instituto de Investigacao e Inovacao em Saude (Portugal) utilized PLGA-PEG-NH2 from PolySciTech (www.polyscitech.com) (PolyVivo AI058) to generate transferrin decorated nanoparticles for blood-brain-barrier penetration. This research holds promise for improved delivery of medicine to brain tissue for improved treatment of cancer or neural disease such as alzeheimers. Read more: Gomes, Maria Joao, Patrick J. Kennedy, Susana Martins, and Bruno Sarmento. “Delivery of siRNA silencing P-gp in peptide-functionalized nanoparticles causes efflux modulation at the blood–brain barrier.” Nanomedicine 0 (2017). http://www.futuremedicine.com/doi/abs/10.2217/nnm-2017-0023

“Aim: Explore the use of transferrin-receptor peptide-functionalized nanoparticles (NPs) targeting blood–brain barrier (BBB) as siRNA carriers to silence P-glycoprotein (P-gp). Materials & methods: Permeability experiments were assessed through a developed BBB cell-based model; P-gp mRNA expression was evaluated in vitro; rhodamine 123 permeability was assessed after cell monolayer treatment with siRNA NPs. Results: Beyond their ability to improve siRNA permeability through the BBB by twofold, 96-h post-transfection, functionalized polymeric NPs successfully reduced P-gp mRNA expression up to 52%, compared with nonfunctionalized systems. Subsequently, the permeability of rhodamine 123 through the human BBB model increased up to 27%. Conclusion: Developed BBB-targeted NPs induced P-gp downregulation and consequent increase on P-gp substrate permeability, revealing their ability to modulate drug efflux at the BBB.”

PLGA from PolySciTech used as part of development of pH responsive nanoparticles for cancer treatment

One of the fundamental problems with treatment of cancer is that the disease itself is still “part” of the human body. Cancer is simply a portion of the tissue and cells which are growing/proliferating at the wrong rate or in a manner which is damaging other tissues. For most diseases caused by an external pathogen, designing a medicinal treatment is simply a matter of finding an agent which affects the pathogen and not the patient. For example, the antibiotic penicillin prevents synthesis of cell-walls, which are key components of bacteria but not found in human cells. For this reason, penicillin can be easily administered to patients at high systemic doses with minimal concern for side effects. Unfortunately, for cancer, the situation is not so simple. Most agents which act to kill or prevent growth of cancer cells also have similar action on healthy cells, due to the fact both that the disease and the patient are of the same cell-type. For this reason, the few differences between cancer cells and normal cells that do exist are ideal targets to improve the action of therapeutics against cancer while maintaining minimal activity against normal cells. One difference between normal tissues and cancer is that, due to differences in tumor metabolism, the tumor tissues become acidic with pH ~6.5-7 (typical cellular pH is 7.4). This has led to rumors that acidity causes the tumor to grow and that cancer can be prevented, or even cured, simply by consuming pH basic (or so-called “alkaline”) foods. If this was true, then cancer could be cured by simply eating Rolaids or TUMS, which is not the case. It is the growing cancer which generates the acidic environment, not the other way around. This pH variability is one difference between normal tissue and cancerous tissues which can be used for optimizing targeted drug strategies. Recently, researchers working jointly at Purdue University, Fudan University (China), Shenyang Pharmaceutical University (China), and Eli Lilly, utilized PLGA from PolySciTech (www.polyscitech.com) (PolyVivo AP081) to create drug-loaded nanoparticles. These were surface modified to render them pH sensitive for preferential release at low pH. Although they worked well during in-vitro testing, there were problems with components of blood interacting with the coating and altering it preventing the pH effect from being fully utilized during in-vivo research. This is an important aspect of real science. Often, during development, there are setbacks to overcome which are discovered over the course of the research. This research holds promise for development of improved chemotherapeutics. Read more: Han, Ning, Jun Xu, Liang Pang, Hyesun Hyun, Jinho Park, and Yoon Yeo. “Development of surface-variable polymeric nanoparticles for drug delivery to tumors.” Molecular Pharmaceutics (2017). http://pubs.acs.org/doi/abs/10.1021/acs.molpharmaceut.7b00050

“Abstract: To develop nanoparticle drug carriers that interact with cells specifically in the mildly acidic tumor microenvironment, we produced polymeric nanoparticles modified with amidated TAT peptide via a simple surface modification method. Two types of core poly(lactic-co-glycolic acid) nanoparticles (NL and NP) were prepared with a phospholipid shell as an optional feature and covered with polydopamine that enabled the conjugation of TAT peptide on the surface. Subsequent treatment with acid anhydrides such as cis-aconitic anhydride (CA) and succinic anhydride (SA) converted amines of lysine residues in TAT peptide to β-carboxylic amides, introducing carboxylic groups that undergo pH-dependent protonation and deprotonation. The nanoparticles modified with amidated TAT peptide (NLpT-CA and NPpT-CA) avoided interactions with LS174T colon cancer cells and J774A.1 macrophages at pH 7.4 but restored the ability to interact with LS174T cells at pH 6.5, delivering paclitaxel efficiently to the cells following a brief contact time. In LS174T tumor-bearing nude mice, NPpT-CA showed less accumulation in the lung than NPpT, reflecting the shielding effect of amidation, but tumor accumulation of NPpT and NPpT-CA was equally minimal. Comparison of particle stability and protein corona formation in media containing sera from different species suggests that NPpT-CA has been activated and opsonized in mouse blood to a greater extent than those in bovine serum-containing medium, thus losing the benefits of pH-sensitivity expected from in vitro experiments. Keywords: acid anhydrides; drug delivery; pH sensitive; PLGA nanoparticles; TAT peptide”

PLGA from PolySciTech used as rapamycin eluting coating on magnesium alloy stents for restenosis prevention as part of heart-disease research

A popular treatment for cardiac blockage is angioplasty. Under this treatment, a thin catheter is run up to the affection portion of the heart and then a balloon is expanded near the tip to remove the blockage. A drawback to this technique is that, over time, the affected blood vessel re-narrows unless something is left in place, such as a stent. Over a longer period of time, the tissues of the blood vessel will regrow over the stent and re-block the vessel by a process called restenosis. A wide variety of technologies have been applied to dealing with this issue so as to provide a long-term and effective angioplasty treatment for treating coronary artery diseases which can lead to heart-attacks if the vessel.  Recently, Researchers working jointly at Purdue University, Shanghai Jiao Tong University (China), and Microport Endovascular Co. utilized PLGA from PolySciTech (www.polyscitech.com) (PolyVivo AP122) to generate a drug-loaded coating on the stent which released anti-proliferative rapamycin to prevent restenosis. They tested this coating both on conventional stainless steel surfaces as well as novel magnesium alloys. They analyzed these samples for drug release, polymer degradation, cellular response, and other parameters. They found drug release was accelerated by the magnesium alloy underlayment and that these materials showed superior anti-proliferative capacity relative to stainless steel. This research holds promise to effectively treat coronary artery disease and prevent heart-attacks by maintaining good blood flow through the blood vessels of the heart. Read more:  Shi, Yongjuan, Jia Pei, Lei Zhang, Byung Kook Lee, Yeonhee Yun, Jian Zhang, Zhonghua Li, Song Gu, Kinam Park, and Guangyin Yuan. “Understanding the effect of magnesium degradation on drug release and anti-proliferation on smooth muscle cells for magnesium-based drug eluting stents.” Corrosion Science (2017). http://www.sciencedirect.com/science/article/pii/S0010938X16314433

“Abstract: To understand the possible influence of substrate degradation on the drug-loading system of magnesium alloy-based drug-eluting stents, a rapamycin drug-loading poly(lactic-co-glycolic acid) coating was prepared on Mg-Nd-Zn-Zr stents for a systematic investigation in a phosphate buffer system. Mg degradation accelerated the drug release kinetics prominently, which was mainly attributed to H2 evolution in the diffusion-controlled phase while thereafter to PLGA erosion. Although physiochemical stability of the released rapamycin was partially deteriorated by magnesium degradation, the drug-loading system on magnesium substrates exhibited a more potent long-term inhibition on smooth muscle cell proliferation in vitro as compared to drug-loaded stainless steel. Highlights: We firstly reported that the degradation of magnesium substrate would improve the in vitro rapamycin release from drug-loading PLGA/RAPA system on a Mg-Nd-Zn-Zr alloy. We quantitatively analyzed the factors enhancing the in vitro drug release kinetics from Mg-based drug-eluting system, distinguishing that it was mainly caused by H2 evolution, while pH only played a trivial role. We reported for the first time that the Mg-based PLGA/RAPA drug-loading system exhibited more pronounced long-term inhibition for the proliferation of smooth muscle cells, under conditions that PLGA with low degradation rate was used as the drug carrier. Keywords Magnesium; Organic coatings; Polymer; Erosion; Interfaces; Kinetic parameters.”