Cancer nanoparticle-based photodynamic therapy developed using mPEG-PLA from PolySciTech

Treating cancer is complicated by several features of the disease including metastasis, drug-resistance, and biological similarity of cancerous cells to healthy ones. Conventional chemotherapy is typically effective at killing cancer cells, however it lacks the capacity to discriminate between cancerous cells and healthy ones. This is where combination therapies can have an advantage. For phototherapy, instead of delivering a toxic molecule (such as cisplatin or paclitaxel) a photosensitizer is delivered. This molecule is inactive, unless it is activated by a very specific frequency of light which activates it killing the cell. The overall method here is to systematically deliver the photosensitizer to a patient and then selectively illuminate the portion where the cancer is located so only the cancer is affected. Recently, researchers working jointly at Northeastern University, George Washington University, and Wenzhou Medical University utilized mPEG-PLA from PolySciTech (www.polyscitech.com) (PolyVivo AK021) to create protoporphyrin IX (a photosensitizer) loaded nanoparticles. They combined these with photodynamic therapy and tested this system as a treatment for melanoma.  This research holds promise to improve the treatment of melanoma, especially malignant or drug-resistant forms. Read more: Wang, Mian, Benjamin M. Geilich, Michael Keidar, and Thomas J. Webster. “Killing malignant melanoma cells with protoporphyrin IX-loaded polymersome-mediated photodynamic therapy and cold atmospheric plasma.” International Journal of Nanomedicine 12 (2017): 4117. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5459981/

“Abstract: Traditional cancer treatments contain several limitations such as incomplete ablation and multidrug resistance. It is known that photodynamic therapy (PDT) is an effective treatment for several tumor types especially melanoma cells. During the PDT process, protoporphyrin IX (PpIX), an effective photosensitizer, can selectively kill cancer cells by activating a special light source. When tumor cells encapsulate a photosensitizer, they can be easily excited into an excited state by a light source. In this study, cold atmospheric plasma (CAP) was used as a novel light source. Results of some studies have showed that cancer cells can be effectively killed by using either a light source or an individual treatment due to the generation of reactive oxygen species and electrons from a wide range of wavelengths, which suggest that CAP can act as a potential light source for anticancer applications compared with UV light sources. Results of the present in vitro study indicated for the first time that PpIX can be successfully loaded into polymersomes. Most importantly, cell viability studies revealed that PpIX-loaded polymersomes had a low toxicity to healthy fibroblasts (20% were killed) at a concentration of 400 µg/mL, but they showed a great potential to selectively kill melanoma cells (almost 50% were killed). With the application of CAP posttreatment, melanoma cell viability significantly decreased (80% were killed) compared to not using a light source (45% were killed) or using a UV light source (65% were killed). In summary, these results indicated for the first time that PpIX-loaded polymersomes together with CAP posttreatment could be a promising tool for skin cancer drug delivery with selective toxicity toward melanoma cells sparing healthy fibroblasts. Keywords: melanoma, polymersomes, protoporphyrin IX, cold atmospheric plasma, photo-dynamic therapy”

PLA from PolySciTech used as precursor for synthesis of environmentally-safe adhesives

Adhesives are used for manufacturing just about everything in our everyday lives. Most of these are petroleum-based materials, which creates an environmental concern due to their chemical off-gassing and lack of degradability. There is an increasing push in polymer science to replace non-degradable synthetics, or petroleum-based materials, with more sustainable alternatives. This becomes increasingly necessary as there is only a limited amount of landfill space available. Poly(lactic acid) (PLA) is a biodegradable polymer which naturally hydrolyzes into non-toxic lactic acid upon contact with water. Lactic acid itself is actually edible (it’s the ingredient that gives Korean kimchi its distinctive tangy-flavor) and can be easily metabolized by a wide variety of organisms back into carbon dioxide and water. For this reason, PLA is a very environmentally safe alternative in comparison to other polymers. However, typical PLA is not considered an adhesive. Recently, researchers at Purdue University utilized several PLAs from PolySciTech (www.polyscitech.com) (PolyVivo Cat# AP035, AP114, and AP138) as precursors to synthesize environmentally-safe poly(lactide)-catechol based adhesives. This research holds promise for the creation of environmentally safe alternatives to petroleum-type adhesives. Read more: Jenkins, Courtney L., Heather M. Siebert, and Jonathan J. Wilker. “Integrating Mussel Chemistry into a Bio-Based Polymer to Create Degradable Adhesives.” Macromolecules (2017). http://pubs.acs.org/doi/abs/10.1021/acs.macromol.6b02213

“Adhesives releasing carcinogenic formaldehyde are almost everywhere in our homes and offices. Most of these glues are permanent, preventing disassembly and recycling of the components. New materials are thus needed to bond and debond without releasing reactive pollutants. In order to develop the next generation of advanced adhesives we have turned to biology for inspiration. The bonding chemistry of mussel proteins was combined with preformed poly(lactic acid), a bio-based polymer, by utilizing side reactions of Sn(oct)2, to create catechol-containing copolymers. Structure–function studies revealed that bulk adhesion was comparable to that of several petroleum-based commercial glues. Bonds could then be degraded in a controlled fashion, separating substrates gradually using mild hydrolysis conditions. These results show that biomimetic design principles can bring about the next generation of adhesive materials. Such new copolymers may help replace permanent materials with renewable and degradable adhesives that do not create chronic exposure to toxins.”

PolySciTech PLGA-PEG-PLGA thermogel used in development of equine anti-fungal treatment to prevent blindness both in humans and horses

Keratomycosis, is a vision-threatening disease which occurs both in horses and humans. Horses, in particular, tend to be extremely sensitive to fungal diseases such as this and have similar pathology to humans. Voriconazole is commonly applied as an anti-fungal drug, but ocular administration is complicated by poor absorption, tear-excretion, and other factors which make high frequency repeat doses necessary. Unsurprisingly, horses do not typically like to receive eye-drops and administering medicine by this method is not a trivial task. There is a need to generate an extended release formulation for their treatment. Recently, researchers at Auburn University, and University of Queensland (Australia) utilized PLGA-PEG-PLGA thermogels from PolySciTech (www.polyscitech.com) (PolyVivo AK024, and AK019) to generate a Voriconazole loaded thermogel. They tested this gel formulation for delivery kinetics and safety. This research holds promise to provide treatment for this disease which can lead to blindness in both humans and horses. Read more: Cuming, Rosemary S., Eva M. Abarca, Sue Duran, Anne A. Wooldridge, Allison J. Stewart, William Ravis, R. Jayachandra Babu, Yuh-Jing Lin, and Terri Hathcock. “Development of a Sustained-Release Voriconazole-Containing Thermogel for Subconjunctival Injection in Horses Subconjunctival Voriconazole-Thermogel.” Investigative Ophthalmology & Visual Science 58, no. 5 (2017): 2746-2754. http://iovs.arvojournals.org/article.aspx?articleid=2629760

“Abstract: Purpose: To determine in vitro release profiles, transcorneal permeation, and ocular injection characteristics of a voriconazole-containing thermogel suitable for injection into the subconjunctival space (SCS). Methods: In vitro release rate of voriconazole (0.3% and 1.5%) from poly (DL-lactide-co-glycolide-b-ethylene glycol-b-DL-lactide-co-glycolide) (PLGA-PEG-PLGA) thermogel was determined for 28 days. A Franz cell diffusion chamber was used to evaluate equine transcorneal and transscleral permeation of voriconazole (1.5% topical solution, 0.3% and 1.5% voriconazole-thermogel) for 24 hours. Antifungal activity of voriconazole released from the 1.5% voriconazole-thermogel was determined via the agar disk diffusion method. Ex vivo equine eyes were injected with liquid voriconazole-thermogel (4°C). Distension of the SCS was assessed ultrasonographically and macroscopically. SCS voriconazole-thermogel injections were performed in a horse 1 week and 2 hours before euthanasia and histopathologic analysis of ocular tissues performed. Results: Voriconazole was released from the PLGA-PEG-PLGA thermogel for more than 21 days in all groups. Release followed first-order kinetics. Voriconazole diffused through the cornea and sclera in all groups. Permeation was greater through the sclerae than corneas. Voriconazole released from the 1.5% voriconazole-thermogel showed antifungal activity in vitro. Voriconazole-thermogel was easily able to be injected into the dorsal SCS where it formed a discrete gel deposit. Voriconazole-thermogel was easily injected in vivo and did not induce any adverse reactions. Conclusions: Voriconazole-containing thermogels have potential application in treatment of keratomycosis. Further research is required to evaluate their performance in vivo.”

PolySciTech PLGA-NH2 used in study on nanoparticle biotransport: Nanoparticle transport explained using a kitten and a football game.

Nanoparticles are small… really small. To put it in perspective, a typical human cell ranges in size from 30-100 um in diameter. Nanoparticles range in size from 1 um down to 0.001 um (0.1 um being common) which means that a typical cell is between 300-1000 times the size of a nanoparticle. To put that in perspective, if a nanoparticle was the size of a kitten (~30 cm) then a human cell would close to the size of a football field (~90-100 M). One important question in science is how to get the kitten onto the football field… er… I mean… how to get the nanoparticle into the cell. This is important because nanoparticles can be loaded with medicines that have a variety of therapeutic effects which can be leveraged only if the nano-kitten can make it onto the cellular football field to make the game-winning kick. There’s two basic ways for either to happen. 1. Active targeting: For our metaphor we’ll assume nano-kitty has a game-day ticket which he politely presents at the front gate for entrance. Similarly, nanoparticles can be specifically conjugated to a specific signal molecule that has the right configuration to allow the nanoparticle access through the cellular membrane by accepted channels. (or) 2. Passive-targeting: This simply relies on the really small nano-kitten simply squeezing through a fence and slipping onto the football field ‘unseen’ due to its small size. Similarly, nanoparticles can sometimes enter cells simply because of their small size. A recent study using PST polymers focused on examining the processes at play in passive-targeting. In addition to final-products used directly for research, PolySciTech (www.polyscitech.com) provides a wide array of intermediates which can be used as precursors for making the final materials. For example, amine-endcap activated PLGA-NH2 has the capability to be chemically conjugated to a wide variety of molecules using common laboratory techniques such as carbodiimide-type conjugation between the PLGA-amine and a NHS-activated carboxylic acid on the other molecule. Recently, researchers at Johns Hopkins University utilized PLGA-NH2 (PolyVivo Cat# AI051) as part of an investigation into nanoparticle transport into living cells. They took the PLGA-NH2 and conjugated on a ‘caged’ rhodamine dye that did not fluoresce until it was prepared to do so by exposure to UV-light. This clever technique allowed the researchers to encapsulate the dye completely within the nanoparticles and precisely track and characterize the nanoparticles during cellular uptake studies. This research holds promise to improve nanotherapeutic formulations for treating a wide-variety of diseases. Read more: Schuster, Benjamin S., Daniel B. Allan, Joshua C. Kays, Justin Hanes, and Robert L. Leheny. “Photoactivatable fluorescent probes reveal heterogeneous nanoparticle permeation through biological gels at multiple scales.” Journal of Controlled Release (2017). http://www.sciencedirect.com/science/article/pii/S0168365917306302

“Abstract: Diffusion through biological gels is crucial for effective drug delivery using nanoparticles. Here, we demonstrate a new method to measure diffusivity over a large range of length scales – from tens of nanometers to tens of micrometers – using photoactivatable fluorescent nanoparticle probes. We have applied this method to investigate the length-scale dependent mobility of nanoparticles in fibrin gels and in sputum from patients with cystic fibrosis (CF). Nanoparticles composed of poly(lactic-co-glycolic acid), with polyethylene glycol coatings to resist bioadhesion, were internally labeled with caged rhodamine to make the particles photoactivatable. We activated particles within a region of sample using brief, targeted exposure to UV light, uncaging the rhodamine and causing the particles in that region to become fluorescent. We imaged the subsequent spatiotemporal evolution in fluorescence intensity and observed the collective particle diffusion over tens of minutes and tens of micrometers. We also performed complementary multiple particle tracking experiments on the same particles, extending significantly the range over which particle motion and its heterogeneity can be observed. In fibrin gels, both methods showed an immobile fraction of particles and a mobile fraction that diffused over all measured length scales. In the CF sputum, particle diffusion was spatially heterogeneous and locally anisotropic but nevertheless typically led to unbounded transport extending tens of micrometers within tens of minutes. These findings provide insight into the mesoscale architecture of these gels and its role in setting their permeability on physiologically relevant length scales, pointing toward strategies for improving nanoparticle drug delivery.Keywords: Photoactivation; Fibrin; Cystic fibrosis; Nanoparticle; Drug delivery; Particle tracking; FRAP; Fluorescence microscopy; Diffusion. (Dye Conjugation protocol): Caged rhodamine-NHS ester and PLGA-NH2 were conjugated through formation of an amide bond. (Conjugating the dye to polymer in this way, rather than encapsulating the dye in the particles, reduces the likelihood of free dye being released.) Briefly, 90 mg of PLGA-NH2 was added to 5 mg of caged rhodamine-NHS ester, leading to a slight molar excess of dye compared to PLGA, 1.23:1, and put under vacuum for 1 h. The mixture was then flushed with nitrogen gas, dissolved in 500 μl of anhydrous dichloromethane (DCM), and reacted for 12 h at room temperature under nitrogen gas. Additional DCM was added as needed to facilitate transfer into 10 ml of − 20 °C diethyl ether to precipitate the product. The PLGA, now conjugated with the caged rhodamine, was washed twice in cold ether by centrifugation. Excess ether was decanted off and the final product, the purified PLGA-caged rhodamine, was placed in a lyophilizer (FreeZone 4.5 Plus; Labconco) for 12 h. The dried product was stored at − 20 °C in a shielded container to prevent exposure to incident UV light. It is important to note that the amide bond is formed between the amine end-cap of the PLGA and the succinimidyl (NHS) ester on the rhodamine; that is, the dye itself and not the ortho-nitroveratryloxycarbonyl (NVOC) cage is directly conjugated to PLGA. Thus, when the photolytic reaction occurs upon exposure to UV light, only the caging group is cleaved, and free dye is not released”

Recent Patent features use of Aquagel for Weight-control application

Recently published patent details the use of Aquagel from PolySciTech (www.polyscitech.com) for use as a weight-control device to prevent over-eating. Read more: Mintchev M, Yadid-Pecht O, Fattouche M, inventors; Eat Little Inc., assignee. Ingestible implement for weight control. United States patent US 9,579,227. 2017 Feb 28. https://www.google.com/patents/US9579227

“ABSTRACT: An orally administrable implement for expanding in a stomach of an animal, including a mammal, to fill a space in the stomach, is provided for weight control. The implement includes: a fluid-permeable expandable container having a first dimension and a second dimension; and a plurality of clusters comprising a swellable material contained within the container and capable of swelling when contacted with a fluid; whereby when the implement is ingested, the fluid in the stomach enters the container causing the clusters therein to swell and the container to expand from the first dimension to the second dimension.”

PLA from PolySciTech used in fundamental study on polymer solubility

Hansen solubility parameters have been used for decades to determine polymer solubility. In most cases, these parameters, based on the various solvent-polymer attraction forces, do provide for prediction of polymer solubility in a given solvent. However, there are instances where the polymers do not interact with solvents in a way predicted by these parameters and understanding the cause of these differences requires more fundamental research. Recently, researchers at The National Center for Scientific Research (France) Used PolySciTech (www.polyscitech.com) poly(lactides) of two different molecular weights (PolyVivo AP086 and AP114) along with PMMA and PS and a wide variety of solvents to perform an in-depth study on solvent-polymer interaction looking at both solubility and swelling. This research holds promise for a more fundamental understanding of polymers and solvents which can be applied to a wide range of applications both medical and industrial. Read more: Vayer, Marylène, Alexane Vital, and Christophe Sinturel. “New insights into polymer-solvent affinity in thin films.” European Polymer Journal (2017). http://www.sciencedirect.com/science/article/pii/S0014305716316512

“Abstract: Polymer-solvent affinity, estimated from the Hansen solubility parameters (HSP), was compared to experimental results of dissolution and swelling of polymer prepared in the specific form of thin film. This was carried out for 3 common polymers (PS, PLA, PMMA) and a series of 16 polar and non-polar solvents. The affinity properties predicted from the calculation of the relative energy distance (RED) values of most of the studied solvent/polymer pairs were in relative good agreement with the dissolution tests performed on the film. In contrast, no clear correlation between the RED and the swelling behavior was found. The observed deviations were attributed to the inability of the HSP theory derived from data acquired in polymer solutions to be extrapolated to the particular case of swollen polymer film. Highlights: Polymer/solvent affinity was estimated using Hansen solubility parameters. Polymer-solvent affinity was evaluated using swelling of polymer thin films. Three polymers PS, PLA and PMMA and 16 solvents were tested. Discrepancies between estimation and experimental results were highlighted. Keywords: polymer thin film; Hansen solubility parameters; swelling; polymer-solvent affinity.”

Fundamental nanoparticle-biological interaction research performed using PLGA-PEG-PLGA from PolySciTech

Although there have been several papers focusing on polymer nanoparticles for drug-delivery applications, there still remains much to be learned about the biological fate of these delivery systems in a fundamental sense aside from specific formulations. Recently, researchers working jointly at University of Ss Cyril and Methodius (Macedonia), CIC biomaGUNE (Spain), Wroclaw University of Science and Technology (Poland), University College Dublin (Ireland), Royal College of Surgeons in Ireland, and Alkaloid AD (Macedonia) utilized PolySciTech (www.polyscitech.com) PLGA-PEG-PLGA block polymers of different sizes (PolyVivo AK017 and PolyVivo AK032) to generate nanoparticles and then assay them for bio-transport and cellular uptake. This fundamental research holds promise to improve nanoparticle delivery systems in general by improving the understanding of their biological interactions. Read more: Dimchevska, Simona, Nikola Geskovski, Rozafa Koliqi, Nadica Matevska-Geskovska, Vanessa Gomez Vallejo, Boguslaw Szczupak, Eneko San Sebastian et al. “Efficacy assessment of self-assembled PLGA-PEG-PLGA nanoparticles: correlation of nano-bio interface interactions, biodistribution, internalization and gene expression studies.” International Journal of Pharmaceutics (2017). http://www.sciencedirect.com/science/article/pii/S0378517317304660

“Abstract: The aim of our study was to develop and compare the biological performance of two types of biodegradable SN-38 loaded nanoparticles (NPs) with various surface properties, composed of low and high Mw triblock PLGA-PEG-PLGA copolymers, applying rational quality and safety by design approach. Therefore, along with the optimization of crucial physico-chemical properties and in order to evaluate the therapeutical potential and biocompatibility of prepared polymeric nanoparticles, analysis of nano-bio interactions, cell internalization, gene expression and biodistribution studies were performed. The optimized formulations, one of low Mw and one composed of high Mw PLGA-PEG-PLGA copolymer, exhibited different characteristics in terms of surface properties, particle size, zeta potential, drug loading, protein adsorption and biodistribution, which may be attributed to the variations in nano-bio interface interactions due to different NP building blocks length and Mw. On the contrary to protein adsorption and biodistribution studies, both types of NPs exhibited similar results during cell internalization and gene expression studies performed in cell culture medium containing serum proteins. This pool of useful data for internalization and efficacy as well as the notable advance in the circulation time of low Mw NPs may be further employed for shaping the potential of the designed nanocarriers. Keywords: polymeric nanoparticles; 7-ethyl-10-hydroxycamptotecin (SN-38); PLGA-PEG-PLGA/PEO-PPO-PEO; nanoprecipitation; nano-bio interface interactions; gene expression”

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”