期刊
INTERNATIONAL JOURNAL OF PHARMACEUTICS
卷 519, 期 1-2, 页码 11-21出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ijpharm.2017.01.011
关键词
Albumin; Nanoparticle; Colloidal stability; Systemic performance; Breast cancer
资金
- National Research Foundation of Korea (NRF) grant - Korea government (MSIP) [2015R1A2A2A01004118, 2015R1A2A2A04004806]
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.
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