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Layer-by-layer assembly of hierarchical nanoarchitectures to enhance the systemic performance of nanoparticle albumin-bound paclitaxel

Title
Layer-by-layer assembly of hierarchical nanoarchitectures to enhance the systemic performance of nanoparticle albumin-bound paclitaxel
Author
최한곤
Keywords
Albumin; Nanoparticle; Colloidal stability; Systemic performance; Breast cancer; DRUG-DELIVERY; ANTITUMOR EFFICACY; IN-VIVO; MICELLES; RELEASE; DOXORUBICIN; CHITOSAN; CANCER; IRINOTECAN; TAXANE
Issue Date
2017-01
Publisher
ELSEVIER SCIENCE BV
Citation
INTERNATIONAL JOURNAL OF PHARMACEUTICS, v. 519, No. 1-2, Page. 11-21
Abstract
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.
URI
https://www.sciencedirect.com/science/article/pii/S037851731730011Xhttp://repository.hanyang.ac.kr/handle/20.500.11754/71610
ISSN
0378-5173; 1873-3476
DOI
10.1016/j.ijpharm.2017.01.011
Appears in Collections:
COLLEGE OF PHARMACY[E](약학대학) > PHARMACY(약학과) > Articles
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