Wednesday, May 4, 2016

PolyVivo PLGA-PEG-NH2 uses as part of investigation of drug-tumor penetration model

PolySciTech division of Akina, Inc. (www.polyscitech.com) provides a wide array of biodegradable block copolymers and reactive intermediates such as PLGA-PEG-NH2 (PolyVivo AI058). Recently, this polymer was used by researchers at The University of Utah and Fuji Research Laboratories as part of developing a tumor model for tracking intra-cellular transportation of drug molecules and delivery systems. This research holds promise for developing advanced chemotherapeutics in the future which allow for higher drug uptake into the tumor cells than what is currently available. Read more about this here: Suzuki, Hidenori, and You Han Bae. "Evaluation of drug penetration with cationic micelles and their penetration mechanism using an in vitro tumor model." Biomaterials (2016). http://www.sciencedirect.com/science/article/pii/S0142961216301569

“Abstract: Elevated interstitial fluid pressure (IFP) and abnormal extracellular matrix (ECM) are major factors causing significant barriers to penetration of nanomedicines in solid tumors. To better understand the barriers, various in vitro tumor models including multicellular spheroids and multilayered cell cultures (MCCs) have been developing. Recently, we have established a unique in vitro tumor model composed of a MCC and an Ussing chamber system which is modified to add a hydraulic pressure gradient through the MCC. In this study, we evaluated the drug penetration ability of cationic micelles using the unique in vitro tumor model. The doxorubicin (DOX)-loaded cationic micelles, which are formed from a triblock copolymer of poly(D,L-lactide-co-glycolide)-block-branched polyethyleneimine-block-poly(D,L-lactide-co-glycolide), deeply penetrated and released the DOX throughout the MCC against convectional flow caused by a hydraulic pressure gradient. The studies using endocytosis markers and inhibitors showed that the micelles utilized mainly macropinocytosis as an internalization pathway. Furthermore, the penetration was apparently inhibited by treatment with exocytosis inhibitor Exo1. These results suggest that the active penetration of the cationic micelles is induced by iterative transcytosis via macropinocytosis and exocytosis. Our findings could be beneficial information to improve intratumoral penetration in new nanomedicines for solid tumors.  Keywords: intratumoral; penetration; multilayered cell culture; micelle; cationic surface; transcytosis”
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