TY - JOUR AU - 최한곤 DA - 2017/01 PY - 2017 UR - https://www.sciencedirect.com/science/article/pii/S037851731730011X UR - https://repository.hanyang.ac.kr/handle/20.500.11754/71610 AB - Although protein-bound paclitaxel (PTX, Abraxane (R)) has been established as a standard PTX-based therapy against multiple cancers, its clinical success is limited by unfavorable pharmacokinetics, suboptimal biodistribution, and acute toxicities. In the present study, we aimed to apply the principles of a layer-by-layer(LbL) technique to improve the poor colloidal stability and pharmacokinetic pattern of nanoparticle albumin-bound paclitaxel (nab-PTX). LbL-based nab-PTX was successfully fabricated by the alternate deposition of polyarginine (pARG) and poly(ethylene glycol)-block-poly(L-aspartic acid) (PEGb-PLD) onto an albumin conjugate. The presence of protective entanglement by polyamino acids prevented the dissociation of nab-PTX and improved its colloidal stability even at a 100-fold dilution. The combined effect of high nanoparticle internalization and controlled release of PTX from LbL-nab-PTX increased its cytotoxicity in MCF-7 and MDA-MB-231 breast cancer cells. LbL-nab-PTX consistently induced apoptosis in approximately 52% and 22% of MCF-7 and MDA-MB-231 cancer cells, respectively. LbL assembly of polypeptides effectively prevented exposure of PTX to the systemic environment and thereby inhibited drug-induced hemolysis. Most importantly, LbL assembly of polypeptides to nab-PTX effectively increased the blood circulation potential of PTX and improved therapeutic efficacy via a significantly higher area under the curve (AUC)(0-infinity). We report for the first time the application of LbL functional architectures for improving the systemic performance of nab-PTX with a view toward its clinical translation for cancer therapy. (C) 2017 Elsevier B.V. All rights reserved. PB - ELSEVIER SCIENCE BV KW - Albumin KW - Nanoparticle KW - Colloidal stability KW - Systemic performance KW - Breast cancer KW - DRUG-DELIVERY KW - ANTITUMOR EFFICACY KW - IN-VIVO KW - MICELLES KW - RELEASE KW - DOXORUBICIN KW - CHITOSAN KW - CANCER KW - IRINOTECAN KW - TAXANE TI - Layer-by-layer assembly of hierarchical nanoarchitectures to enhance the systemic performance of nanoparticle albumin-bound paclitaxel IS - 1-2 VL - 519 DO - 10.1016/j.ijpharm.2017.01.011 T2 - INTERNATIONAL JOURNAL OF PHARMACEUTICS ER -