John Garner's Technical Blog
John GarnerJohn Garner, Manager

What's New and on the Manager's Mind

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


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PolySciTech mPEG-PLGA/PLGA-rhodamine used in the development of nanoparticle-based intracellular MRSA treatment

Tuesday, August 15, 2017, 4:07 PM ET

MRSA is a bacterial infection that is highly resistant to conventional antibiotic treatments or other therapies. It is still affected by vancomycin, but the bacterial spores have the capability to ‘hide’ inside of cells making it very difficult to treat. One means around this is to use nanoparticles for delivery of the antibiotic to the cells to ensure suitable vancomycin in a local concentration to kill off the bacteria. Recently, researchers at Purdue University used mPEG-PLGA (Polyvivo AK030) and rhodamine-B labelled PLGA (PolyVivo AV011) from PolySciTech (www.polyscitech.com) to create pH sensitive nanoparticles designed for intracellular delivery of vancomycin. This research holds promise to improve treatments of this deadly bacterial infection. Read more: Pei, Yihua, Mohamed F. Mohamed, Mohamed N. Seleem, and Yoon Yeo. "Particle engineering for intracellular delivery of vancomycin to methicillin-resistant Staphylococcus aureus (MRSA)-infected macrophages." Journal of Controlled Release (2017). http://www.sciencedirect.com/science/article/pii/S0168365917307745

“Abstract: Methicillin-resistant Staphylococcus aureus (MRSA) infection is a serious threat to the public health. MRSA is particularly difficult to treat when it invades host cells and survive inside the cells. Although vancomycin is active against MRSA, it does not effectively kill intracellular MRSA due to the molecular size and polarity that limit its cellular uptake. To overcome poor intracellular delivery of vancomycin, we developed a particle formulation (PpZEV) based on a blend of polymers with distinct functions: (i) poly(lactic-co-glycolic acid) (PLGA, P) serving as the main delivery platform, (ii) polyethylene glycol-PLGA conjugate (PEG-PLGA, p) to help maintain an appropriate level of polarity for timely release of vancomycin, (iii) Eudragit E100 (a copolymer based on dimethylaminoethyl methacrylate, butyl methacrylate and methyl methacrylate, E) to enhance vancomycin encapsulation, and (iv) a chitosan derivative called ZWC (Z) to trigger pH-sensitive drug release. PpZEV NPs were preferentially taken up by the macrophages due to its size (500–1000 nm) and facilitated vancomycin delivery to the intracellular pathogens. Accordingly, PpZEV NPs showed better antimicrobial activity than free vancomycin against intracellular MRSA and other intracellular pathogens. When administered intravenously, PpZEV NPs rapidly accumulated in the liver and spleen, the target organs of intracellular infection. Therefore, PpZEV NPs is a promising carrier of vancomycin for the treatment of intracellular MRSA infection. Keywords: Nanoparticles, Intracellular drug delivery, pH-sensitive, Macrophages, Intracellular MRSA, Vancomycin”

Improved targeted-delivery system using oriented antibody fragments developed using PLGA-PEG-Azide from PolySciTech.

Monday, August 14, 2017, 2:43 PM ET

A powerful tool for medicinal delivery is the use of a nanoparticle with a surface covered in a specific antibody or targeting ligand. Because these antibodies and ligands bind specifically to certain protein factors these can be tailored to target to specific cells, notably cancer cells. Since antibody bonding is a stereochemical process, shape and orientation of the antibody matters in terms of its capability to bind. If the active site of the ligand is facing inwards, towards the nanoparticle, it may not work well at all. Recently, researchers working at Queen's University Belfast, University College London, (UK) and Universidade de Lisboa (Portugal) used PLGA-PEG-Azide from PolySciTech (www.polyscitech.com, PolyVivo AI085) to generate nanoparticles which had very precisely controlled antibody orientation on their surface allowing for improved functionality and targeting. They tested this system for its ability to bind to HER2 (a factor that is overexpressed in cancer cells) and found it had substantially higher binding than a randomly oriented nanoparticle system. This research holds promise for developing a wide-array of targeted delivery systems for treating a variety of diseases, most notably cancer. Read more: M. Greene, D. A. Richards, J. Nogueira, K. Campbell, P. Smyth, M. Fernandez, C. J. Scott and V. Chudasama “Generating Next-Generation Antibody-Nanoparticle Conjugates through the Oriented Installation of Non-Engineered Antibody Fragments” Chem. Sci., 2017, DOI: 10.1039/C7SC02747H. (http://pubs.rsc.org/en/Content/ArticleLanding/2017/SC/C7SC02747H#!divAbstract)

“Abstract: The successful development of targeted nanotherapeutics is contingent upon the conjugation of therapeutic nanoparticles to target-specific ligands, with particular emphasis being placed on antibody-based ligands. Thus, new methods that enable the covalent and precise installation of targeting antibodies to nanoparticle surfaces are greatly desired, especially those which do not rely on costly and time-consuming antibody engineering techniques. Herein we present a novel method for the highly controlled and oriented covalent conjugation of non-engineered antibody F(ab) fragments to PLGA-PEG nanoparticles using disulfide-selective pyridazinedione linkers and strain-promoted alkyneazide click chemistry. Exemplification of this method with trastuzumab and cetuximab showed significant improvements in both conjugation efficiency and antigen binding capability, when compared to commonly employed strategies for antibody-nanoparticle construction. This new approach paves the way for the development of antibody-targeted nanomedicines with improved paratope availability, reproducibility and uniformity to enhance both biological activity and ease of manufacture.”

PolySciTech PLGA-NH2 used in research thesis on nanoparticle-surface interactions with living cells

Friday, August 11, 2017, 3:35 PM ET

Nanoparticles have been around for many years but we are still, as a species, just scratching at the surface of understanding them. Of course, the surface is the most important part of a nanoparticle since, due to their incredibly small size, they have an incredible surface area to volume ratio. For example, 1g of PLGA nanoparticles (100 nm) would have a surface area of 7.8 square meters (a little larger than a typical parking space for a car). For this reason, the surface and how it interacts with living organisms is the most important aspect of nanoparticle technology. Recently, Angie (Morris) Thorn at University of Iowa published a PhD thesis which details efforts to broaden our understanding of nanoparticle surface interactions with cells. This includes work with PLGA-NH2 (PolyVivo AI063) from PolySciTech (www.polyscitech.com) to generate nanoparticles covered with either chitosan (for mucoadhesion) or TPP (mitochondria-targeting) to create targeted nanoparticles as drug-delivery vectors. Read more: Thorn, Angie Sue Morris. "The impact of nanoparticle surface chemistry on biological systems." (2017). http://ir.uiowa.edu/etd/5659/

“Abstract: The unique properties of nanomaterials, such as their small size and large surface area-to-volume ratios, have attracted tremendous interest in the scientific community over the last few decades. Thus, the synthesis and characterization of many different types of nanoparticles has been well defined and reported on in the literature. Current research efforts have redirected from the basic study of nanomaterial synthesis and their properties to more application-based studies where the development of functionally active materials is necessary. Today such nanoparticle-based systems exist for a range of biomedical applications including imaging, drug delivery and sensors. The inherent properties of the nanomaterial, although important, aren’t always ideal for specific applications. In order to optimize nanoparticles for biomedical applications it is often desirable to tune their surface properties. Researchers have shown that these surface properties (such as charge, hydrophobicity, or reactivity) play a direct role in the interactions between nanoparticles and biological systems can be altered by attaching molecules to the surface of nanoparticles. In this work, the effects of physicochemical properties of a wide variety of nanoparticles was investigated using in vitro and in vivo models. For example, copper oxide (CuO) nanoparticles were of interest due to their instability in biological media. These nanoparticles undergo dissolution when in an aqueous environment and tend to aggregate. Therefore, the cytotoxicity of two sizes of CuO NPs was evaluated in cultured cells to develop a better understanding of how these propertied effect toxicity outcomes in biological systems. From these studies, it was determined that CuO NPs are cytotoxic to lung cells in a size-dependent manner and that dissolved copper ions contribute to the cytotoxicity however it is not solely responsible for cell death. Moreover, silica nanoparticles are one of the most commonly used nanomaterials because they are easy to synthesize and their properties (such as size, porosity and surface chemistry) can be fine-tuned. Silica nanoparticles can be found in thousands of commercially available products such as toothpastes, cosmetics and detergents and are currently being developed for biomedical applications such as drug delivery and biomedical imaging. Our findings herein indicate that the surface chemistry of silica nanoparticles can have an effect on lung inflammation after exposure. Specifically, amine-modified silica NPs are considered to be less toxic compared to bare silica nanoparticles. Together, these studies provide insight into the role that material properties have on toxicity and allow for a better understanding of their impact on human and environmental health. The final aim of this thesis was to develop surface-modified nanoparticles for drug delivery applications. For this, biodegradable, polymeric NPs were used due to their inert nature and biocompatibility. Furthermore, polymeric NPs are excellent for loading drugs and using them as drug delivery vehicles. In this work, poly (lactic-co-glycolic acid) (PLGA) NPs were loaded with a therapeutic peptide. These NPs were then coated with chitosan (a mucoadhesive polymer) for the treatment of allergic asthma or coated with a small cationic mitochondrial targeting agent for the treatment of ischemia/reperfusion injury. Taken as a whole, this thesis sheds light on the impact of NPs on human health. First by providing useful toxological data for CuO and silica NPs as well as highlighting the potential of surface-modified polymeric NPs to be used in drug delivery-based applications. Keywords: Cell Culture, Nanoparticle, Toxicity”

PEG-PLGA/PLGA from PolySciTech used by Precision NanoSystems, Inc. as part of microfluidics NanoAssemblr™ method optimization and testing

Friday, July 28, 2017, 3:09 PM ET

Microfluidics references the use of systems which have extremely small fluid-channels on the order of magnitude of microns in scale. Precision NanoSystems, Inc. is a company which has developed an array of microfluidic instruments and machines designed for a variety of applications including the synthesis of micro and nanoparticles. For generating micro/nano-particles of polymers, the typical process is to dissolve the polymer in an organic solvent and then mix it with water so that the polymer (which is not water soluble) precipitates out into sub-micron sized particles. Unlike simple emulsion, where the solvent and water are randomly mixed together, the mixing of the organic phase with the water phase in a microfluidics system is highly controlled which allows for the generation of very precise micro/nanoparticles. Recently, Precision Nanosystems, Inc. used a series of mPEG-PLGA’s from PolySciTech (www.polyscitech.com, PolyVivo AK010, AK037, AK106) to make a series of test pegylated nanoparticles with highly controlled properties. They reported these results in a scientific poster presented at controlled release society (CRS) 2017 meeting. This research holds promise for a wide array of applications involving the use of nanoparticles/microparticles as drug delivery systems. Read more here: S.M. Garg, M. Parmar, A. Thomas, E. Ouellet, M. Deleonardis, P. Johnson, A. Armstead, S. Ip, T.J. Leaver, A.W. Wild, R.J. Taylor, E.C. Ramsay “Microfluidics-based Manufacture of PEG-b-PLGA Block Copolymer Nanoparticles for the Delivery of Small Molecule Therapeutics” Controlled Release Society 2017 Poster Session. (https://www.precisionnanosystems.com/resources/?_sf_s=PEG-b-PLGA&_sft_resource-type=poster)

“(Poster introduction): Purpose: In recent years, numerous methods have been developed for the production of block copolymer nanoparticles as drug delivery vehicles. However, these methods pose numerous challenges in maintaining consistent nanoparticle quality, tuning size depending on the application, optimization for scale-up, and reproducibility. The NanoAssemblr™ platform is an automated microfluidics-based system that eliminates user variability and is capable of reproducible, and scalable manufacture of nanoparticles. Here, we describe the use of microfluidic mixing to manufacture PEG-b-PLGA nanoparticles using the NanoAssemblr™ Benchtop instrument. We further describe optimization strategies and investigate the physical encapsulation of a hydrophobic model drug coumarin-6.Results: Microfluidic mixing enabled the rapid and consistent manufacturing of PEG-b-PLGA nanoparticles having diameters below 100 nm. Instrument parameters such as aqueous:organic Flow Rate Ratio and Total Flow Rate had a significant impact on the size of the resulting nanoparticles. Increasing the molecular weight of the PLGA block from 10000 - 95000 Da resulted in an increase in the size of the nanoparticles from 40 - 80 nm. However, changes in the total flow rate of the instrument enabled all the nanoparticles to be tuned to a similar size of 60 nm which is difficult to control using conventional techniques. Coumarin-6 was successfully loaded into PEG-b-PLGA nanoparticles with an encapsulation efficiency of 52% w/w which was significantly higher than that obtained by co-solvent evaporation technique (34% w/w). The size of the nanoparticles prepared using the NanoAssemblr platform were tunable over a broad range while co-solvent evaporation does not provide a reliable means to tune size.”

In addition to this poster, Precision Nanosystems, Inc. has utilized PLGA from PolySciTech (PolyVivo AP121) in generating a wide array of technical data relevant to their microfluidic system. You can see these technical whitepapers here (https://www.precisionnanosystems.com/resources/?_sf_s=plga&_sft_resource-type=tech-bulletins-and-white-papers)

PLA-amine from PolySciTech used in development of atherosclerosis-targeted nanoparticles for treatment of heart disease

Tuesday, July 25, 2017, 2:27 PM ET

Heart disease, typically due to atherosclerotic lesions, is one of the leading causes of death in USA. Most treatments for this disease focus on surgical interventions (e.g. stent placement), which is often utilized in acute situations, or on systemic medicines such as statins, which are typically applied as a preventative. There is a need for therapies to be applied in non-emergency situations but where atherosclerotic lesions are known to be present. Conventionally, nanoparticles have been applied for use against cancer, however they can be targeted to lesions by using appropriate targeting moieties. Recently, researchers working jointly at Harvard Medical School, New York University, Technical University of Denmark, Korea Institute of Ceramic Engineering and Technology, Korea Advanced Institute of Science and Technology, and King Abdulaziz University used PLA-NH2 (PolyVivo AI041, www.polyscitech.com) from PolySciTech as a reactive precursor for generating a fluorescently-conjugated tracer as part of a novel nanoparticle-based system for treatment of artherosclerosis. Read more: Yu, Mikyung, Jaume Amengual, Arjun Menon, Nazila Kamaly, Felix Zhou, Xiaoding Xu, Phei Er Saw et al. "Targeted Nanotherapeutics Encapsulating Liver X Receptor Agonist GW3965 Enhance Antiatherogenic Effects without Adverse Effects on Hepatic Lipid Metabolism in Ldlr−/− Mice." Advanced Healthcare Materials (2017). http://onlinelibrary.wiley.com/doi/10.1002/adhm.201700313/full

“Abstract: The pharmacological manipulation of liver X receptors (LXRs) has been an attractive therapeutic strategy for atherosclerosis treatment as they control reverse cholesterol transport and inflammatory response. This study presents the development and efficacy of nanoparticles (NPs) incorporating the synthetic LXR agonist GW3965 (GW) in targeting atherosclerotic lesions. Collagen IV (Col IV) targeting ligands are employed to functionalize the NPs to improve targeting to the atherosclerotic plaque, and formulation parameters such as the length of the polyethylene glycol (PEG) coating molecules are systematically optimized. In vitro studies indicate that the GW-encapsulated NPs upregulate the LXR target genes and downregulate proinflammatory mediator in macrophages. The Col IV-targeted NPs encapsulating GW (Col IV–GW–NPs) successfully reaches atherosclerotic lesions when administered for 5 weeks to mice with preexisting lesions, substantially reducing macrophage content (≈30%) compared to the PBS group, which is with greater efficacy versus nontargeting NPs encapsulating GW (GW–NPs) (≈18%). In addition, mice administered the Col IV–GW–NPs do not demonstrate increased hepatic lipid biosynthesis or hyperlipidemia during the treatment period, unlike mice injected with the free GW. These findings suggest a new form of LXR-based therapeutics capable of enhanced delivery of the LXR agonist to atherosclerotic lesions without altering hepatic lipid metabolism.”

Protein phosphorylation assay kits by Tymora Analytical now available through PolySciTech

Thursday, July 20, 2017, 9:20 AM ET

The selective phosphorylation of proteins is a key step in many pathways regulating their functions. Abnormal phosphorylation is involved in a wide variety of diseases including cancer. To perform antibody labeling, an effective antibody has to be made for each phosphorylated protein, which is an expensive and time-consuming process. Recently, Tymora Analytical has developed a titanium-based reagent assay kit to allow for detection of protein phosphorylation in a rapid, efficient, and sensitive assay. Due to a recent distribution agreement, these products are now available through PolySciTech division of Akina, Inc. (https://akinainc.com/polyscitech/products/tymora/). Learn more about this powerful assay method in a recent publication here: Iliuk, Anton, Li Li, Michael Melesse, Mark C. Hall, and W. Andy Tao. "Multiplexed Imaging of Protein Phosphorylation on Membranes Based on TiIV Functionalized Nanopolymers." ChemBioChem 17, no. 10 (2016): 900-903. http://europepmc.org/articles/4870103

“Abstract: Accurate protein phosphorylation analysis reveals dynamic cellular signaling events not evident from protein expression levels. The most dominant biochemical assay, western blotting, suffers from the inadequate availability and poor quality of phospho-specific antibodies for phosphorylated proteins. Furthermore, multiplexed assays based on antibodies are limited by steric interference between the antibodies. Here we introduce a multifunctionalized nanopolymer for the universal detection of phosphoproteins that, in combination with regular antibodies, allows multiplexed imaging and accurate determination of protein phosphorylation on membranes. Keywords: antibodies, dendrimers, membranes, multiplexed analysis, phosphoproteins”

CRS Meeting 2017

Friday, July 14, 2017, 4:32 PM ET

Meet PolySciTech (www.polyscitech.com) at booth 501 at the CRS meeting in Boston next week https://www.controlledreleasesociety.org/meetings/annual/Pages/default.aspx

PLGA from PolySciTech used in the development of nanoparticle-based obesity treatment

Wednesday, July 12, 2017, 1:01 PM ET

Obesity in humans is a contributing factor to many other health concerns, such as arthritis and cardiovascular problems. Recently, researchers at Purdue University utilized PLGA from PolySciTech (www.polyscitech.com) (PolyVivo AP101) to develop nanoparticles which deliver dibenzazepine to reduce the overgrowth of adipocytes (fat-cells). This research holds promise to provide for improved treatments of obesity. Read more: Jiang, Chunhui, Mario Alberto Cano-Vega, Feng Yue, Liangju Kuang, Naagarajan Narayanan, Gozde Uzunalli, Madeline P. Merkel, Shihuan Kuang, and Meng Deng. "Dibenzazepine-loaded nanoparticles induce local browning of white adipose tissue to counteract obesity." Molecular Therapy (2017). http://www.cell.com/molecular-therapy-family/molecular-therapy/abstract/S1525-0016(17)30256-3

“Inhibition of Notch signaling via systemic drug administration triggers conversion of white adipocytes into beige adipocytes (browning) and reduces adiposity. However, translation of this discovery into clinical practice is challenged by potential off-target side effects and lack of control over the location and temporal extent of beige adipocyte biogenesis. Here, we demonstrate an alternative approach to stimulate browning using nanoparticles (NPs) composed of FDA-approved poly(lactide-co-glycolide) that enable sustained local release of a Notch inhibitor (dibenzazepine, DBZ). These DBZ-loaded NPs support rapid cellular internalization and inhibit Notch signaling in adipocytes. Importantly, focal injection of these NPs into the inguinal white adipose tissue depots of diet-induced obese mice results in localized NP retention and browning of adipocytes, consequently improving the glucose homeostasis and attenuating body-weight gain of the treated mice. These findings offer new avenues to develop a potential therapeutic strategy for clinical treatment of obesity and its associated metabolic syndrome. Keywords: drug delivery; nanoparticle; browning; adipocyte; Notch signaling; obesity; PLGA; dibenzazepine; adipose tissue; Notch inhibitor”

Tissue scaffolds with improved delivery of growth factor developed using PLGA-PEG-Mal from PolySciTech

Wednesday, July 12, 2017, 1:00 PM ET

A powerful tool in medicine would be the ability to produce a tissue-scaffold which allows for tissue which has been lost due to disease or trauma to be replaced with fresh stem-cells. There are many barriers to the developemtn of this tool one of which is ensuring that the stem-cells have the appropriate anchoring sites as well as the correct growth factors to ensure their appropriate growth and development. Recently, researchers working jointly at Fudan University (China), Tianjin Medical University (China), Ewha Women’s University (Korea), and University of Michigan utilized Maleimide-PEG-PLGA (PolyVivo AI136) and fluorescently conjugated PLGA-FPR648 (Polyvivo AV008) from PolySciTech (www.polyscitech.com) to generate a scaffold which allowed for controlled release of differentiation factors. They used the developed scaffold to repair ischemic tissue in a mouse model. This research holds promise to enable tissue repair and regeneration by successfully growing differentiated stem-cells into damaged areas. Read more: Li, Ruixiang, Zhiqing Pang, Huining He, Seungjin Lee, Jing Qin, Jian Wu, Liang Pang, Jianxin Wang, and Victor C. Yang. "Drug depot-anchoring hydrogel: A self-assembling scaffold for localized drug release and enhanced stem cell differentiation." Journal of Controlled Release (2017). http://www.sciencedirect.com/science/article/pii/S016836591730706X

“Abstract: Localized and long-term delivery of growth factors has been a long-standing challenge for stem cell-based tissue engineering. In the current study, a polymeric drug depot-anchoring hydrogel scaffold was developed for the sustained release of macromolecules to enhance the differentiation of stem cells. Self-assembling peptide (RADA16)-modified drug depots (RDDs) were prepared and anchored to a RADA16 hydrogel. The anchoring effect of RADA16 modification on the RDDs was tested both in vitro and in vivo. It was shown that the in vitro leakage of RDDs from the RADA16 hydrogel was significantly less than that of the unmodified drug depots (DDs). In addition, the in vivo retention of injected hydrogel-incorporated RDDs was significantly longer than that of hydrogel-incorporated unmodified DDs. A model drug, vascular endothelial growth factor (VEGF), was encapsulated in RDDs (V-RDDs) as drug depot that was then anchored to the hydrogel. The release of VEGF could be sustained for 4 weeks. Endothelial progenitor cells (EPCs) were cultured on the V-RDDs-anchoring scaffold and enhanced cell proliferation and differentiation were observed, compared with a VEGF-loaded scaffold. Furthermore, this scaffold laden with EPCs promoted neovascularization in an animal model of hind limb ischemia. These results demonstrate that self-assembling hydrogel-anchored drug-loaded RDDs are promising for localized and sustained drug release, and can effectively enhance the proliferation and differentiation of resident stem cells, thus lead to successful tissue regeneration. Graphical abstract: Schematic illustration of a vascular endothelial growth factor (VEGF)-loaded RDDs-anchoring hydrogel. The RADA16 peptide is the basic self-assembling unit forming fiber and constructing hydrogel; poly (lactic-co-glycolic acid) (PLGA) based, VEGF-loaded drug depots (DDs) were modified using the RADA16 peptide (V-RDDs) to anchor them to the skeleton of the hydrogel; PEG was applied as a spacer to ensure the full stretch of the RADA16 peptide. VEGF demonstrated sustained release into the hydrogel to enhance the proliferation and differentiation of resident EPCs. Keywords: PLGA; RADA16 hydrogel; Sustained release; Endothelial progenitor cells; Vascular endothelial growth factor; Tissue regeneration”

mPEG-PLGA from PolySciTech used in development of immune-control treatment for allergic reactions

Wednesday, July 12, 2017, 12:56 PM ET

Allergic contact dermatitis is a common inflammatory skin condition caused by a pathological immune response to a given trigger such as poison ivy oils or nickel metal. This aggravating skin condition can be prevented and treated by reducing the local formation of allergen specific t-cells. Doing so, however, requires careful localized delivery of specific set of molecules including proteins and small-molecule signals to discourage an overly responsive immune attack. This same strategy has great application towards other uses such as autoimmune disease disorders and transplant rejection. Recently, Researchers at University of Pittsburgh used mPEG-PLGA from PolySciTech (www.polyscitech.com) (PolyVivo AK037) to generate microparticles which can locally deliver TGF-β1, Rapamycin, and IL-2 to the skin. They discovered these particles were successful in prevent or reversing allergic responses in sensitized mice. This research holds promise to treat a wide-array of immune-mediated disease state. Read more: Balmert, Stephen C., Cara Donahue, John R. Vu, Geza Erdos, Louis D. Falo, and Steven R. Little. "In vivo induction of regulatory T cells promotes allergen tolerance and suppresses allergic contact dermatitis." Journal of Controlled Release (2017). http://www.sciencedirect.com/science/article/pii/S0168365917307046

“Abstract: Allergic contact dermatitis (ACD) is a common T-cell mediated inflammatory skin condition, characterized by an intensely pruritic rash at the site of contact with allergens like poison ivy or nickel. Current clinical treatments use topical corticosteroids, which broadly and transiently suppress inflammation and symptoms of ACD, but fail to address the underlying immune dysfunction. Here, we present an alternative therapeutic approach that teaches the immune system to tolerate contact allergens by expanding populations of naturally suppressive allergen-specific regulatory T cells (Tregs). Specifically, biodegradable poly(ethylene glycol)-poly(lactic-co-glycolic acid) (PEG-PLGA) microparticles were engineered to release TGF-β1, Rapamycin, and IL-2, to locally sustain a microenvironment that promotes Treg differentiation. By expanding allergen-specific Tregs and reducing pro-inflammatory effector T cells, these microparticles inhibited destructive hypersensitivity responses to subsequent allergen exposure in an allergen-specific manner, effectively preventing or reversing ACD in previously sensitized mice. Ultimately, this approach to in vivo Treg induction could also enable novel therapies for transplant rejection and autoimmune diseases.”

mPEG-PLGA from PolyScitech used in development of dual-drug nanotherapy treatment for non-small cell lung cancer

Friday, July 7, 2017, 4:04 PM ET

Non-small cell lung cancer is an extremely prevelant type of cancer with over 200K cases in the USA per year. Typically it is treated using chemotherapy and radiotherapy, but the incidence of reoccurrence is quite high after these therapies. Recently, researchers working jointly at University of North Carolina, Tiangin Vocational Institute (China), Westminster College, China Medical University, and Peking Union Medical College (China) used mPEG-PLGA from PolySciTech (www.polyscitech.com) (PolyVivo AK029) to develop a co-encapsulated nanoparticle loaded with paclitaxel and a cisplatin prodrug. They applied this to a mouse model of lung cancer and found the particles reduced tumor growth more effectively than loose drug administration. This research holds promise to improve the treatment of lung cancer. Read more: Jing Tian, Yuanzeng Min, Zachary Rodgers, Kin Man Au, Charles Tilden Hagan, Maofan Zhang, Kyle Roche, Feifei Yang, Kyle Thomas Wagner and Andrew Z Wang “Co-delivery of paclitaxel and cisplatin with biocompatible PLGA-PEG nanoparticles enhances chemoradiotherapy in non-small cell lung cancer models.” J. Mater. Chem. B, 2017, Accepted Manuscript. DOI 10.1039/C7TB01370A http://pubs.rsc.org/en/content/articlelanding/2017/tb/c7tb01370a#!divAbstract

“Abstract: Chemoradiotherapy (CRT) with paclitaxel (PTX) and cisplatin (CP) is part of the standard of care for patients with locally advanced non-small cell lung cancer (NSCLC). Despite the high treatment intensity, many patients still develop local recurrence after treatment. Thus, there is a strong need to further improve CRT for lung cancer. One strategy is to co-deliver cytotoxic chemotherapy agents using biocompatible nanoparticles (NPs) which can limit off-target tissue toxicity and improve therapeutic efficacy. Herein, we report the development of dual-drug loaded nanoformulations that improve the efficacy of CRT for NSCLC by co-encapsulation of cisplatin (CP) and PTX in PLGA-PEG NPs. Mice bearing NSCLC xenografts given the dual-drug loaded NPs during CRT showed greater inhibition of tumor growth than free drug combinations or combinations of single-drug loaded NPs. These results indicate that using a NP co-delivery strategy for this common CRT regimen may improve clinical responses in NSCLC patients. Supplementary details http://www.rsc.org/suppdata/c7/tb/c7tb01370a/c7tb01370a1.pdf

Akina, Inc. Closed for Independence Day.

Tuesday, July 4, 2017, 10:39 AM ET

Akina, Inc. is closed for USA independence day July 4th. We will reopen from July 5th. Any orders placed will be processed then.

Immunotherapy research using PLGA, PLGA-PEG-maleimide, and PLGA-rhodamine from PolySciTech shows promise for cancer treatment

Monday, July 3, 2017, 2:23 PM ET

Treatment of cancer remains difficult due to a wide variety of reasons. One problem is that, typically, cancer tends to metastasize and spread so that there are smaller tumors, tendrils or clumps of tumor cells instead of a singular, lone cancer tumor. These ‘satellite tumors’ can remain even after the main tumor has been removed by surgery or other process. Radiation and chemotherapy treatments can affect nearby cancer cells, by the absopal effect, but this effect is relatively weak and often these smaller tumor portions regrow to form new cancer tumors. A good strategy for destroying cancer, both main tumor and nearby satellite tumors, is to utilize immunotherapy. This process effectively ‘vaccinates’ the body so that the immune system attacks the cancer as if it is an invasive pathogen. Recently, researchers working jointly at University of North Carolina, Duke University, Xuzhou Medical University (Japan), North Carolina Sate University, and the Memorial Sloan-Kettering Cancer Center developed a novel antigen-capturing-nanoparticle based immunotherapy treatment for cancer treatment. This therapy relies on nanoparticles capturing the antigens from the tumor and then presenting those to immunce cells to elicit an immune response. For this research, they used PLGA (AP059), mPEG-PLGA (AK037), PLGA-PEG-NH2 (AI058), PLGA-PEG-Mal (AI052) and poly(lactide-co-glycolide)-rhodamine B (AV011) from PolySciTech (www.polyscitech.com) to generate these nanoparticles and to track them by fluorescence, respectively. This research holds promise for improved cancer therapy. Read more: Min, Yuanzeng, Kyle C. Roche, Shaomin Tian, Michael J. Eblan, Karen P. McKinnon, Joseph M. Caster, Shengjie Chai et al. "Antigen-capturing nanoparticles improve the abscopal effect and cancer immunotherapy." Nature Nanotechnology (2017). (https://www.nature.com/nnano/journal/vaop/ncurrent/full/nnano.2017.113.html)

“Immunotherapy holds tremendous promise for improving cancer treatment1. To administer radiotherapy with immunotherapy has been shown to improve immune responses and can elicit the ‘abscopal effect’. Unfortunately, response rates for this strategy remain low. Herein we report an improved cancer immunotherapy approach that utilizes antigen-capturing nanoparticles (AC-NPs). We engineered several AC-NP formulations and demonstrated that the set of protein antigens captured by each AC-NP formulation is dependent on the NP surface properties. We showed that AC-NPs deliver tumour-specific proteins to antigen-presenting cells (APCs) and significantly improve the efficacy of αPD-1 (anti-programmed cell death 1) treatment using the B16F10 melanoma model, generating up to a 20% cure rate compared with 0% without AC-NPs. Mechanistic studies revealed that AC-NPs induced an expansion of CD8+ cytotoxic T cells and increased both CD4+T/Treg and CD8+T/Treg ratios (Treg, regulatory T cells). Our work presents a novel strategy to improve cancer immunotherapy with nanotechnology. Subject terms: Drug delivery Nanotechnology in cancer”

PolySciTech certificates of analysis now available directly on the website

Monday, June 26, 2017, 1:28 PM ET

All materials generated by the PolySciTech division of Akina, Inc. (www.polyscitech.com) undergo a rigorous set of chemical characterization tests. These typically include Fourier-transform infrared spectrophotometry (FTIR) scan, proton nuclear magnetic resonance (HNMR), and gel-permeation chromatography (GPC). The FTIR test gives information on specific chemical moieties included in the material based on their particular absorption peaks/bands. The HNMR test provides further chemical characterization by providing peaks which correspond to specific shifts based on hydrogen local environment. This also allows for proton-counting to be used for determining polymer features. For example the lactide-to-glycolide ratio in PLGA can be determined by comparing the peak integration at 5.2 ppm (1H, lactide) with the integration at 4.8 (2H, glycolide). Gel-permeation chromatography yields data on the molecular weight of the polymer as well as the distribution of polymer chain lengths. The data from these tests are shown directly on the certificate of analysis (COA) to provide the customer with a thorough set of chemical characterization data. Recently, Akina, Inc. has compiled the COAs for both currently available batches as well as historical batches of material into an online, searchable format. This allows for pulling up data both on historical batches purchased some time ago as well as reviewing COAs for current materials. Note that, as long as enough material is in stock to fill the order, you can request a specific batch on an order at no additional charge by indicating the batch on the order or in the ‘Special notes’ section on the online order form. See the searchable set of COAs here (https://akinainc.com/polyscitech/products/polyvivo/COA.php)

Synthesize like a pro with reactive intermediates generated by award-winning researchers

Friday, June 23, 2017, 4:28 PM ET

Akanocure Pharmaceuticals, a Purdue University spin-off company, has won several awards including the Purdue Ag-celerator award, FOUNDER.org award, as well as has been a finalist in the MassChallenge Boston competition. This company, founded by Sherine Abdelmawla, Mohammad Noshi, and Philip Fuchs, generates novel synthetic methodologies to recreate naturally occurring compounds. These synthetic compounds can be used for a wide-variety of therapeutic applications including cancer treatments. The process begins with specific precursors that have defined stereochemistry so that the exact chiral-structure of the molecule is defined ensuring appropriate bioactivity. These custom-developed precursors are lactone derivatives with precisely controlled protecting units at specific locations, can be utilized to generate a broad range of molecules. These unique chemicals are commercially distributed through Akina, Inc. PolySciTech Division (https://akinainc.com/polyscitech/products/akanocure/index.php) and can be used in your lab for generating a wide array of bioactive molecules. (Photo from www.purduefoundry.com/news)

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

Tuesday, June 20, 2017, 1:36 PM ET

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

Wednesday, June 14, 2017, 2:53 PM ET

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

Thursday, June 8, 2017, 2:16 PM ET

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.

Tuesday, June 6, 2017, 11:16 AM ET

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

Thursday, June 1, 2017, 3:19 PM ET

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

Thursday, June 1, 2017, 3:18 PM ET

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

Thursday, June 1, 2017, 3:16 PM ET

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

Wednesday, May 31, 2017, 4:11 PM ET

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

Friday, May 26, 2017, 1:43 PM ET

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

Friday, May 26, 2017, 11:33 AM ET

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”

These posts are syndicated from John Garner's blog at http://jgakinainc.blogspot.com/.

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