Monthly Archives: March 2015

Akina, Inc. hydrogel template technique used for dexamethasone-PLGA microparticle generation

PolySciTech (www.polyscitech.com) provides a wide array of research supplies. In addition to polymers there are hydrogel template kits and related accessories available (https://akinainc.com/polyscitech/currentResearch/microparticleFormulation/index.php) recently these kits were used to generate dexamethasone loaded microparticles and tested for treatment of vocal fold scarring. Read more: Kosinski, Aaron M., Jewel M. Pothen, Alyssa Panitch, and M. Preeti Sivasankar. “Dexamethasone Controlled Release on TGF-β1 Treated Vocal Fold Fibroblasts.” Annals of Otology, Rhinology & Laryngology (2015): 0003489415570933. http://aor.sagepub.com/content/early/2015/02/07/0003489415570933.abstract

“Abstract:  Objective: Corticosteroids may be beneficial in treating vocal fold scarring. Current drug delivery methods do not permit controlled corticosteroid release. Here we investigate the effects of poly-lactic-co-glycolic acid (PLGA) microparticles loaded with the corticosteroid dexamethasone in reducing collagen synthesis and inflammation in vocal fold fibroblasts treated with and without TGF-β1. Study Design: Experimental, in vitro study. Methods: PLGA microparticles of differing molecular weight and terminating moieties were synthesized using a hydrogel template method. The release of dexamethasone was characterized from these microparticles over 4 days. Based on the release studies, ester-terminated low molecular weight PLGA microparticles were loaded with dexamethasone and applied to TGF-β1 treated vocal fold fibroblasts for 4 days. Quantitative polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assays (ELISAs) were used to assess the effects of released dexamethasone on collagen synthesis and inflammatory mediators. Results: COL3A1 and COL1A2 were significantly down-regulated after exposure to ester-terminated low molecular weight PLGA microparticles loaded with dexamethasone. The loaded microparticles also reduced interleukin-6 synthesis. Conclusion: These data show promise in using a PLGA microparticle-based delivery system to control dexamethasone release over 4 days. Our findings lay the groundwork for developing more effective treatments for vocal fold scarring.”

PolySciTech mPEG-PLA (PolyVivo AK09) used for cancer treatment/staining

PolySciTech (www.polyscitech.com) provides a wide array of biodegradable block copolymers. Recently a publication utilized PolyVivo AK09 as part of a system for imaging and targeting tumor cells. Read more: Rapoport, Natalya, Roohi Gupta, Yoo-Shin Kim, and Brian E. O’Neill. “Polymeric Micelles and nanoemulsions as tumor-targeted drug carriers: Insight through intravital imaging.” Journal of Controlled Release (2015). http://www.sciencedirect.com/science/article/pii/S0168365915001662

“Abstract: Intravital imaging of nanoparticle extravasation and tumor accumulation has revealed, for the first time, detailed features of carrier and drug behavior in circulation and tissue that suggest new directions for optimization of drug nanocarriers. Using intravital fluorescent microscopy, the extent of the extravasation, diffusion in the tissue, internalization by tissue cells, and uptake by the RES system were studied for polymeric micelles, nanoemulsions, and nanoemulsion-encapsulated drug. Discrimination of vascular and tissue compartments in the processes of micelle and nanodroplets extravasation and tissue accumulation was possible. A simple 1-D continuum model was suggested that allowed discriminating between various kinetic regimes of nanocarrier (or released drug) internalization in tumors of various sizes and cell density. The extravasation and tumor cell internalization occurred much faster for polymeric micelles than for nanoemulsion droplets. Fast micelle internalization resulted in the formation of a perivascular fluorescent coating around blood vessels. A new mechanism of micelle extravasation and internalization was suggested, based on the fast extravasation and internalization rates of copolymer unimers while maintaining micelle/unimer equilibrium in the circulation. The data suggested that to be therapeutically effective, nanoparticles with high internalization rate should manifest fast diffusion in the tumor tissue in order to avoid generation of concentration gradients that induce drug resistance. However an extra-fast diffusion should be avoided as it may result in the flow of extravasated nanoparticles from the tumor to normal organs, which would compromise targeting efficiency. The extravasation kinetics were different for nanodroplets and nanodroplet-encapsulated drug F-PTX suggesting a premature release of some fraction of the drug from the carrier. In conclusion, the development of an “ideal” drug carrier should involve the optimization of both drug retention and carrier diffusion parameters. Keywords: drug delivery; perfluorocarbon; nanodroplets; micelles; paclitaxel; nanoparticle extravasation; nanoparticle diffusion; intravital microscopy”

Rapaport, 2015 fluorescent tumor polyvivo micelle

Thermogelling Glycol Chitin for progesterone delivery

PolySciTech (www.polyscitech.com) is the USA distributor of thermogelling glycol chitin. A recent publication has come out highlighting the usage of this material for drug delivery formulations including vaginal delivery of progesterone. Read more: Almomen, Aliyah, Sungpil Cho, Chieh-Hsiang Yang, Zhengzheng Li, Elke A. Jarboe, C. Matthew Peterson, Kang Moo Huh, and Margit M. Janát-Amsbury. “Thermosensitive Progesterone Hydrogel: A Safe and Effective New Formulation for Vaginal Application.” Pharmaceutical Research (2015): 1-14. http://link.springer.com/article/10.1007/s11095-014-1616-8

“Abstract: Purpose: The safe and functional delivery of progesterone through the vaginal route remains an unmet clinical need. The purpose of this work is to prepare a new progesterone (P4) gel for vaginal application using a thermosensitive mucoadhesive polymer, glycol chitin (GC). Method: Thermogelling, mucoadhesive, mechanical, and viscoelastic properties of GC and the new formulation were evaluated using rheometry. In vitro release profile and the bioactivity of P4 were determined using vaginal fluid simulant (VFS) pH 4.2, and PR-reporter gene assay, respectively. In vitro safety of the formulations was tested using (VK2/E6E7) vaginal epithelial cell line and Lactobacillus Crispatus. Finally, in vivo safety and the efficacy of this formulation were evaluated using an endometrial hypoplasia mouse model. Results: Results shows the aqueous solution of 5%; (w/v) GC loaded with 0.1%; (w/v) P4 prepared in pH 4.2, (GC-P4), forms a thermosensitive mucoadhesive hydrogel and can maintain stable physical properties at 37°C. GC-P4 gel release 50% of P4 in 4 h after exposure to VFS, and no significant decrease in % viability of VK2/E6E7 or Lactobacillus was found after exposure to 5% GC or GC-P4. GC-P4 does not exhibit obvious toxicities to vaginal tissue in vivo even after repeated application. Efficacy studies indicated that GC-P4 was capable of preventing the progression of simple endometrial hyperplasia (SEH) to complex atypical endometrial hyperplasia (CAEH) in vivo. Conclusions: Results indicates that GC-P4 retains many characteristics for an effective vaginal delivery system for P4. Therefore we believe that GC-P4 formulation is a promising alternative to current vaginal P4 formulation.”

New Research Product Line: 3DCellMaker

A new product line is available from PolySciTech:Akina and this one is 3DCellMaker (www.3DCellMaker.com). 3DCellMaker is a thermogelling synthetic substrate which allows for the easy growth of cells in a 3D pattern without requiring the use of complex hanging drop, magnetism, or other techniques. The unique polymer formulation allows for 3DCellMaker to be mixed at low temperature (5-10C) with media generating a self-gelling system capable of aiding the growth of tumors and other cells into 3D shapes such as spheroids. There are two versions available. One is optimized for seeding the cells on top of the solidified gel while the other is optimized for seeding the cells in the cold-liquid gel and then warming to transition. In both cases the gel sets and allows the cells to grow in a 3D pattern over the course of 2-12 days after which time the gel is washed away. This system allows for easy generation of a more accurate representation of cancer cell modeling than tradition 2D flat plate and at a lower price than xenograft models. No specialized equipment is required for 3DCellMaker as it can generate spheroids in any conventional well-plate or other typical incubation plasticware in a typical 5% CO2/37C incubator regardless of container properties or geometric orientation.

3DCellMaker spheroid MCF7 cells

New Product PCL-b-PEI AO43

PolySciTech (www.polyscitech.com) provides a wide array of block copolymers. Recently we have launched new product AO43 which is PCL-b-PEI (40,000-800) which allows for delivery of anionic molecules such as RNA/DNA. This product is to replace AO06 which was also a PCL-PEI however the block weight of PCL was lower which inhibited reproducible DCM solubility of the product. See product listing here: https://akinainc.com/polyscitech/products/polyvivo/catalogue.php?highlight=AO43#h

PCL-b-PEI

PLGA from PolySciTech used for investigating blood interactions with metal alloys

PolySciTech (www.polyscitech.com) provides a wide array of biodegradable polymers including PLGA. Recently PLGA from PolySciTech was used for investigation of blood compatibility. Read more: Nguyen, Thanh Yen, Aaron F. Cipriano, Ren‐Guo Guan, Zhan‐Yong Zhao, and Huinan Liu. “In vitro interactions of blood, platelet, and fibroblast with biodegradable magnesium‐zinc‐strontium alloys.” Journal of Biomedical Materials Research Part A (2015). http://onlinelibrary.wiley.com/doi/10.1002/jbm.a.35429/full

“Abstract: Magnesium (Mg) alloy is an attractive class of metallic biomaterial for cardiovascular applications due to its biodegradability and mechanical properties. In this study, we investigated the degradation in blood, thrombogenicity, and cytocompatibility of Magnesium-Zinc-Strontium (Mg-Zn-Sr) alloys, specifically four Mg-4 wt % Zn-xSr (x = 0.15, 0.5, 1, and 1.5 wt %) alloys, together with pure Mg control and relevant reference materials for cardiovascular applications. Human whole blood and platelet rich plasma (PRP) were used as the incubation media to investigate the degradation behavior of the Mg-Zn-Sr alloys. The results showed that the PRP had a greater pH increase and greater concentration of Mg2+ ions when compared with whole blood after 2 h of incubation with the same respective Mg alloys, suggesting that the Mg alloys degraded faster in PRP than in whole blood. The Mg alloy with 4 wt % Zn and 0.15 wt % Sr (named as ZSr41A) was identified as the most promising alloy for cardiovascular stent applications, because it showed slower degradation and less thrombogenicity, as indicated by the lower concentrations of Mg2+ ions released and less deposition of platelets. Additionally, ZSr41 alloys were cytocompatible with fibroblasts in direct exposure culture in which the cells adhered and proliferated around the samples, with no statistical difference in cell adhesion density compared with the blank reference. Future studies on the ZSr41 alloys are necessary to investigate their direct interactions with other important cells in cardiovascular system, such as vascular endothelial cells and smooth muscle cells. Keywords: magnesium-zinc-strontium alloys;biodegradable Mg-Zn-Sr alloys;blood;platelet;fibroblast;in vitro culture;cardiovascular applications”

mPEG-PLGA and mal-PEG-PLGA from PolySciTech used for Toremifene delivery to prostate cancer

PolySciTech (www.polyscitech.com) provides a wide array of block copolymers and reactive intermediates including mPEG-PLGA and maleimide-PEG-PLGA copolymers. A recent article from Albany College utilized these polymers to generate a targeted nanoparticle carrier for delivery of toremifene to prostate cancer. Read more: Hariri, Waseem, Thangirala Sudha, Dhruba J. Bharali, Huadong Cui, and Shaker A. Mousa. “Nano-Targeted Delivery of Toremifene, an Estrogen Receptor-α Blocker in Prostate Cancer.” Pharmaceutical Research (2015): 1-11. http://link.springer.com/article/10.1007/s11095-015-1662-x

“ABSTRACT: Purpose: Estrogen Receptor-α (ERα) expression is increased in prostate cancer and acts as an oncogene. We propose that blocking of estrogen hormone binding to ERα using the ERα blocker toremifene will reduce the tumorigenicity of prostate cancer, and nano-targeted delivery of toremifene will improve anticancer efficacy. We report the synthesis and use in an orthotopic mouse model of PLGA-PEG nanoparticles encapsulating toremifene and nanoparticles encapsulating toremifene that are also conjugated to anti-PSMA for targeted prostate tumor delivery. Methods: Human prostate cancer cell line PC3M and a nude mouse model were used to test efficacy of nano-targeted and nano-encapsulated toremifene versus free toremifene on the growth and differentiation of tumor cells. Results: Treatment with free toremifene resulted in a significant reduction in growth of prostate tumor and proliferation, and its nano-targeting resulted in greater reduction of prostate tumor growth, greater toremifene tumor uptake, and enhanced tumor necrosis. Tumors from animals treated with nano-encapsulated toremifene conjugated with anti-PSMA showed about a 15-fold increase of toremifene compared to free toremifene. Conclusions: Our data provide evidence that blocking ERα by toremifene and targeting prostate cancer tissues with anti-PSMA antibody on the nanoparticles’ surface repressed the tumorigenicity of prostate cancer cells in this mouse model.”

PLGA-PEG used for ultra-sound guided nanoparticle RNA delivery to tumor cells

PolySciTech (www.polyscitech.com) provides a wide array of PEG-PLGA copolymers including PLGA-PEG-COOH (e.g. PolyVivo AI34). Recently these types of polymers were used for development of a combinatorial drug delivery system based on ultrasound and microRNA loaded PLGA-PEG nanoparticles. Read more: Wang, Tzu-Yin, Jung Woo Choe, Kanyi Pu, Rammohan Devulapally, Sunitha Bachawal, Steven Machtaler, Sayan Mullick Chowdhury et al. “Ultrasound-guided delivery of microRNA loaded nanoparticles into cancer.” Journal of Controlled Release 203 (2015): 99-108. Full-Text: http://www-kyg.stanford.edu/khuriyakub/opencms/Downloads/15_Wang_01.pdf

“Abstract: Ultrasound induced microbubble cavitation can cause enhanced permeability across natural barriers of tumors such as vessel walls or cellular membranes, allowing for enhanced therapeutic delivery into the target tissues. While enhanced delivery of small (< 1 nm) molecules has been shown at acoustic pressures below 1 MPa both in vitro and in vivo, the delivery efficiency of larger (> 100 nm) therapeutic carriers into cancer remains unclear and may require a higher pressure for sufficient delivery. Enhanced delivery of larger therapeutic carriers such as FDA approved pegylated poly(lactic-co-glycolic acid) nanoparticles (PLGA-PEG-NP) has significant clinical value because these nanoparticles have been shown to protect encapsulated drugs from degradation in the blood circulation and allow for slow and prolonged release of encapsulated drugs at the target location. In this study, various acoustic parameters were investigated to facilitate the successful delivery of two nanocarriers, a fluorescent semiconducting polymer model drug nanoparticle as well as PLGA-PEG-NP into human colon cancer xenografts in mice. We first measured the cavitation dose produced by various acoustic parameters (pressure, pulse length, and pulse repetition frequency) and microbubble concentration in a tissue mimicking phantom. Next, in vivo studies were performed to evaluate the penetration depth of nanocarriers using various acoustic pressures, ranging between 1.7 and 6.9 MPa. Finally, a therapeutic microRNA, miR-122, was loaded into PLGA-PEG-NP and the amount of delivered miR-122 was assessed using quantitative RT-PCR. Our results show that acoustic pressures had the strongest effect on cavitation. An increase of the pressure from 0.8 to 6.9 MPa resulted in a nearly 50-fold increase in cavitation in phantom experiments. In vivo, as the pressures increased from 1.7 to 6.9 MPa, the amount of nanoparticles deposited in cancer xenografts was increased from 4- to 14-fold, and the median penetration depth of extravasated nanoparticles was increased from 1.3-fold to 3-fold, compared to control conditions without ultrasound, as examined on 3D confocal microscopy. When delivering miR-122 loaded PLGA-PEG-NP using optimal acoustic settings with minimum tissue damage, miR-122 delivery into tumors with ultrasound and microbubbles was 7.9-fold higher compared to treatment without ultrasound. This study demonstrates that ultrasound induced microbubble cavitation can be a useful tool for delivery of therapeutic miR loaded nanocarriers into cancer in vivo.”

Wang 2015 PEG-PLGA ultrasound cancer therapy

PolySciTech PLA utilized for development of cell-borne drug delivery system

PolySciTech (www.polyscitech.com) provides a wide array of biodegradable polymers including PLA. Recent research has utilized PolySciTech PLA (PolyVivo AP071) for development of adhesive cell-plate which attaches to a live cell. Read more: Xia, Junfei, Zhibin Wang, Danting Huang, Yuanwei Yan, Yan Li, and Jingjiao Guan. “Asymmetric Biodegradable Microdevices for Cell-borne Drug Delivery.” ACS Applied Materials & Interfaces (2015). http://pubs.acs.org/doi/abs/10.1021/acsami.5b00613

“Abstract: Use of live cells as carriers for drug-laden particulate structures possesses unique advantages for drug delivery. In this work, we report on the development of a novel type of particulate structures called microdevices for cell-borne drug delivery. The microdevices were fabricated by soft lithography with a disk-like shape. Each microdevice was composed a layer of biodegradable thermoplastic such as poly(lactic-co-glycolic acid). One face of the thermoplastic layer was covalently grafted with a cell-adhesive polyelectrolyte such as poly-L-lysine. This asymmetric structure allowed the microdevices to bind to live cells through bulk mixing without causing cell aggregation. Moreover, the cell-microdevice complexes were largely stable, and the viability and proliferation ability of the cells were not affected by the microdevices over a week. In addition, sustained release of a mock drug from the microdevices was demonstrated. This type of microdevices promises to be clinically useful for sustained intravascular drug delivery.”

PLGA-PEG-PLGA incorporating growth factors used for regenerative cell scaffold

PolySciTech (www.polyscitech.com) provides a wide array of triblock PLGA-PEG-PLGA thermogels which includes Polyvivo AK12, AK24, AK92, and others.  Recently these types of polymers were investigated for use as cellular scaffolds when incorporating a variety of growth factors. Read more: Zheng, Ling, Lin Wang, Jie Qin, Xiaolin Sun, Tingting Yang, Yuxin Ni, and Yanmin Zhou. “New Biodegradable Implant Material Containing Hydrogel with Growth Factors of Lyophilized PRF in Combination with an nHA/PLGA Scaffold.” Journal of Hard Tissue Biology 24, no. 1 (2015): 54-60. full-text: https://www.jstage.jst.go.jp/article/jhtb/24/1/24_54/_pdf

“Abstract: The temperature-sensitive triblock copolymer poly-(D, L-lactic acid-co-glycolic acid) (PLGA)-polyethylene glycol (PEG)-PLGA (PLGA-PEG-PLGA) is an FDA-approved material that has the ability to provide a sustained release of drugs and/or proteins. Platelet-rich fibrin(PRF)is second generation platelet concentration that contains growth factors such as transforming growth factor-β1 (TGF-β1), platelet derived growth factor-AB (PDGF-AB), and insulin-like growth factor-I (IGF-I). These growth factors affect the migration and proliferation of diverse cell types, including endothelial cells, smooth muscle cells, and osteoblast-like cells. This study sought to combine the hydrogel into scaffolds in order to serve as a sustained release system for PRF-derived growth factors. Poly (lactic-co-glycolic) acid (PLGA) and nano-hydroxyapatite (nHA) were used to prepare the hydrogel-containing scaffolds with the PRF-derived growth factors. We then investigated the effects of the hydrogel on modulating the activity of osteoblasts in vitro. We indicated that the hydrogel (Gel) was well-distributed in the inner surface of scaffolds, which themselves exhibited relatively interconnected pores with uniform sizes. The addition of the hydrogel didn’t affect their inherently high porosity. In vitro release tests indicated that the system containing nHA/PLGA/Gel/PRF provided for a slow and sustained release of PRF-derived growth factors. The results from our in vitro studies indicated that the MG63 cells cultured with both scaffold media extracts did not appear to have cytotoxic responses, and the nHA/PLGA/Gel/PRF system could improve the adhesion and proliferation of MG63 cells when compared to controls (p < 0.05). This in vitro evaluation suggests that the hydrogel-scaffold system is suitable as a model for bone tissue engineering, and that it allows for the sustained release of growth factors to improve bone reconstruction.”