Monthly Archives: February 2015

PEG-PLGA block copolymer optimized for nanoparticle preparation

PolySciTech (www.polyscitech.com) provides a wide array of mPEG-PLGA polymers. Recently these types of polymers were reported for use in an optimized nanoparticle emulsion method. Read more: Yoneki, Nao, Taku Takami, Tomoki Ito, Ryosuke Anzai, Kengo Fukuda, Keita Kinoshita, Seiichi Sonotaki, and Yoshihiko Murakami. “One-pot facile preparation of PEG-modified PLGA nanoparticles: Effects of PEG and PLGA on release properties of the particles.” Colloids and Surfaces A: Physicochemical and Engineering Aspects (2015). http://www.sciencedirect.com/science/article/pii/S0927775715000291

“Abstract: We show here a one-pot facile preparation of poly(ethylene glycol) (PEG)-modified poly(lactide-co-glycolide) (PLGA) nanoparticles by means of a novel “block copolymer-assisted” emulsification/evaporation method. In the present article, we clarified the effects of preparation conditions and the structural properties of both polymeric modifiers and particle-forming hydrophobic polymers on the properties of the PEG-modified PLGA nanoparticles. We first clarified that the concentration of PLGA, the volume ratio of an organic solvent to a PVA solution, and a stirring rate were major factors affecting the diameter of the nanoparticles. We successfully prepared the nanoparticles, with a diameter of approximately 200 nm under the optimized conditions. The additive amount and the composition of PEG–PLA block copolymers affected the surface charge of the nanoparticles. Finally, we clarified that the compositions and molecular weights of the block copolymers greatly affected the release properties of PEG-modified nanoparticles. Keywords: Nanoparticle; Surface modification; Poly(ethylene glycol) (PEG); Poly(lactide-co-glycolide) (PLGA); Drug delivery system”

Yoneki 2015 emulsion nanoparticle

PLGA from PolySciTech used as control for development of biodegradable metal alloy

PolySciTech (www.polyscitech.com) provides a wide array of PLGA copolymers. Recently PLGA from PolySciTech was used as a control article (known biodegradable material) to compare the development of a biodegradable metal alloy against. 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/abstract

“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 hours 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 to 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-PLA nanoparticles used as part of photo-triggered tumor treatment

PolySciTech (www.polyscitech.com) provides a wide array of mPEG-PLA diblock copolymers for use in generating nanoparticles to improve drug delivery. Recently these types of polymers were used to improve uptake of paclitaxel in tumor-bearing mouse model. Read more: Araki, Tomoya, Ken-ichi Ogawara, Haruka Suzuki, Rie Kawai, Taka-ichi Watanabe, Tsutomu Ono, and Kazutaka Higaki. “Augmented EPR effect by photo-triggered tumor vascular treatment improved therapeutic efficacy of liposomal paclitaxel in mice bearing tumors with low permeable vasculature.” Journal of Controlled Release 200 (2015): 106-114. http://www.sciencedirect.com/science/article/pii/S0168365914008359

“Abstract: The effects of photo-triggered tumor vascular treatment (PVT) on the structural and functional properties of tumor vasculature were assessed in Colon-26 (C26) and B16/BL6 (B16) tumor-bearing mice. Furthermore, anti-tumor efficacy of subsequently injected PEG liposomal paclitaxel (PL-PTX) was also evaluated. As a photosensitizer, a hydrophobic porphyrin derivative was used and formulated in polymeric nanoparticle composed of polyethylene glycol-block-polylactic acid to avoid its non-specific in vivo disposition. In the mice bearing C26 with high permeable vasculature, the prominent anti-tumor activity was confirmed by PVT alone, but the subsequently injected PL-PTX did not show any additive effect. PVT itself initially induced apoptotic cell death of tumor vascular endothelial cells and platelet aggregation, which would have subsequently induced apoptosis of C26 tumor cells surrounding the vasculature. On the other hand, in the mice bearing B16 with low permeable vasculature, PVT enhanced the anti-tumor activity of subsequently injected PL-PTX, which would be attributed to the tumor disposition amount and area of PEG liposomes enhanced by PVT. These results clearly indicated that the treatment would have made it possible to provide more efficient extravasation of PL-PTX, leading to its more potent anti-tumor effect. Keywords: Vascular permeability; Photodynamic treatment; Endothelial cell; Liposome; Cancer chemotherapy”

Tomoya 2015 PVT PEG-PLA cancer treatment

PLGA Nano-carriers used for targeted treatment of atherosclerosis

PolySciTech (www.polyscitech.com) provides a wide array of PLGA and related biodegradable polymers including specialty block copolymers. Recently researchers have coated PLGA nanoparticles with lipid coating that targets to macrophages and atherosclerotic plaque. Read more: Sanchez-Gaytan, Brenda L., Francois Fay, Mark E. Lobatto, Jun Tang, Mireille Ouimet, YongTae Kim, Susanne van der Staay et al. “HDL-mimetic PLGA nanoparticle for the targeting of atherosclerosis plaque macrophages.” Bioconjugate Chemistry (2015). http://pubs.acs.org/doi/abs/10.1021/bc500517k

“Abstract: High-density lipoprotein (HDL) is a natural nanoparticle that exhibits an intrinsic affinity for atherosclerotic plaque macrophages. Its natural targeting capability as well as the option to incorporate lipophilic payloads, e.g., imaging or therapeutic components, in both the hydrophobic core and the phospholipid corona make the HDL platform an attractive nanocarrier. To realize controlled release properties, we developed a hybrid polymer/HDL nanoparticle comprised of a lipid/apolipoprotein coating that encapsulates a poly(lactic-co-glycolic acid) (PLGA) core. This novel HDL-like nanoparticle (PLGA-HDL) displayed natural HDL characteristics, including preferential uptake by macrophages and a good cholesterol efflux capacity, combined with a typical PLGA nanoparticle slow release profile. In vivo studies carried out with an ApoE knockout mouse model of atherosclerosis showed clear accumulation of PLGA-HDL nanoparticles in atherosclerotic plaques, which co-localized with plaque macrophages. This bio-mimetic platform integrates the targeting capacity of HDL bio-mimetic nanoparticles with the characteristic versatility of PLGA based nanocarriers.”

PEG-PLA used to create porous film to encourage cellular growth

PolySciTech (www.polyscitech.com) provides a wide array of PEG-PLA block copolymers. Recently these types of polymers were utilized in order to generate honey-comb shaped films using a templating technique. It was found that these surfaces could support the growth of GFP-U87 cells indicating that these polymers can be a suitable matrix for cell growth. Read more: Yao, Bingjian, Qingzeng Zhu, Linli Yao, and Jingcheng Hao. “Fabrication of honeycomb-structured poly (ethylene glycol)-block-poly (lactic acid) porous films and biomedical applications for cell growth.” Applied Surface Science (2015). http://www.sciencedirect.com/science/article/pii/S0169433215002093

“Abstract: A series of poly(ethylene glycol)-block-poly(lactic acid) (PEG-PLA) copolymers with a hydrophobic PLA block of different molecular weights and a fixed length hydrophilic PEG were synthesized successfully and charaterized. These amphiphilic block copolymers were used to fabricate honeycomb-structured porous films using the breath figure (BF) templating technique. The surface topology and composition of the highly ordered pattern film were further characterized by scanning electron microscopy (SEM), atomic force microscopy (AFM), X-ray photoelectron spectroscopy (XPS) and fluorescence microscopy. The results indicated that the PEG-to-PLA block molecular weight ratio influenced the BF film surface topology. The film with the best ordered pores was obtained with a PEG-to-PLA ratio of 2.0 × 103: 3.0 × 104. The self-organization of the hydrophilic PEG chains within the pores was confirmed by XPS and fluorescence labeled PEG. A model is proposed to elucidate the stabilization process of the amphiphilic PEG-PLA aggregated architecture on the water droplet-based templates. In addition, GFP-U87 cell viability has been investigated by MTS test and the cell morphology on the honeycomb-structured PEG-PLA porous film has been evaluated using phase-contrast microscope. This porous film is shown to be suitable as a matrix for cell growth. Highlights: Honeycomb-structured PEG-PLA porous films were fabricated. The organization of pores depends on molecular weight ratio of PEG-to-PLA block. The pores in the film were internally decorated with a layer of PEG. The honeycomb-structured PEG-PLA film was suitable as a substrate for cell growth. Keywords: Poly(ethylene glycol)-block-poly(lactic acid) (PEG-PLA); Breath figure; Honeycomb-structured film; Migration; Cell growth”

Bingjian, 2015 honeycomb cell PEG-PLA

PLLA-PEG-PLLA/PLLA-PEI-PLLA used for DNA delivery

PolySciTech (www.polyscitech.com) provides a wide array of block copolymers. Recently these types of block copolymers were utilized to generate DNA delivery systems. Read more: Abebe, Daniel G., Rima Kandil, Teresa Kraus, Maha Elsayed, Olivia M. Merkel, and Tomoko Fujiwara. “Three‐Layered Biodegradable Micelles Prepared by Two‐Step Self‐Assembly of PLA‐PEI‐PLA and PLA‐PEG‐PLA Triblock Copolymers as Efficient Gene Delivery System.” Macromolecular Bioscience (2015). http://onlinelibrary.wiley.com/doi/10.1002/mabi.201400488/full

“Abstract: “Three-layered micelles” (3LM) composed of two triblock copolymers, poly(L-lactide)-b-polyethyleneimine-b-poly(L-lactide) (PLLA-PEI-PLLA) and poly(L-lactide)-b-poly(ethylene glycol)-b-poly(L-lactide) (PLLA-PEG-PLLA) are designed to combine electrostatic interaction and solvent-induced condensation of DNA. The low molecular weight PLLA-PEI-PLLA is synthesized by a facile amine-protection/deprotection approach and employed as a gene vector, compacting DNA as a polyplex core in the organo-micelles. The individual organo-micelle is further encapsulated within a PLLA-PEG-PLLA amphiphilic micelle leading to an aqueous stable colloidal dispersion. The resulting spherical 3LM possess a hydrodynamic diameter of ca. 200 nm and zeta potential close to neutral and display excellent stability to competing polyanions such as dextran sulfate in neutral pH (7.4). Such high stability is attributed to the complete shielding of the PEI/DNA polyplex core with an impermeable hydrophobic intermediate layer. However, greater than 90% of the encapsulated DNA are released within 30 min when exposed to slightly acidic pH (4.5). Based on our findings, a new class of non-viral delivery system for nucleic acids with superb stability and stealth. Keywords: block copolymers;gene delivery;micelles;poly(lactic acid);polyethyleneimine.”

Abebe 2015 DNA deliver PLA-PEG-PLA PLA-PEI-PLA

 

PolySciTech PS-P(DL)La copolymer used for nanoparticle anticancer docetaxel delivery

PolySciTech (www.polyscitech.com) provides a wide array of block copolymers. One of these polymers is polystyrene-b-poly(DL)Lactide (AK34).  Recently this polymer was used to develop a nanaoparticle delivery system for docetaxel to prostate cancer cells. Read more: Lee, Jae-Young, Jung Sun Kim, Hyun-Jong Cho, and Dae-Duk Kim. “Poly (styrene)-b-poly (DL-lactide) copolymer-based nanoparticles for anticancer drug delivery.” International journal of nanomedicine 9 (2014): 2803. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4051715/

“Abstract: Poly(styrene)-b-poly(DL-lactide) (PS-PDLLA) copolymer-based nanoparticles (NPs) of a narrow size distribution, negative zeta potential, and spherical shape were fabricated for the delivery of docetaxel (DCT). The particle size was consistently maintained in serum for 24 hours and a sustained drug release pattern was observed for 10 days in the tested formulations. The cytotoxicity of the developed blank NPs was negligible in prostate cancer (PC-3) cells. Cellular uptake and distribution of the constructed NPs containing a hydrophobic fluorescent dye was monitored by confocal laser scanning microscopy (CLSM) for 24 hours. Anti-tumor efficacy of the PS-PDLLA/DCT NPs in PC-3 cells was significantly more potent than that of the group treated with commercially available DCT, Taxotere® (P<0.05). Blood biochemistry tests showed that no serious toxicity was observed with the blank NPs in the liver and kidney. In a pharmacokinetic study of DCT in rats, in vivo clearance of PS-PDLLA/DCT NPs decreased while the half-life in blood increased compared to the Taxotere-treated group (P<0.05). The PS-PDLLA NPs are expected to be a biocompatible and efficient nano-delivery system for anticancer drugs. Keywords: docetaxel, prolonged blood circulation, prostate cancer”