Category Archives: Polymer Basics

This category is for general discussion of the basics of polymer science without regard to a particular usage.

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

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

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”

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

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

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

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

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

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

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

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

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.