Hyaluronic acid-decorated poly(lactic-co-glycolic acid) nanoparticles for combined delivery of docetaxel and tanespimycin

Title
Hyaluronic acid-decorated poly(lactic-co-glycolic acid) nanoparticles for combined delivery of docetaxel and tanespimycin
Author(s)
김종오로샨프라단티르거네쉬라마사미최주연김정환포우델비자이탁진욱나탈리아누콜로바[나탈리아누콜로바]최한곤[최한곤]용철순
Keywords
SELF-ASSEMBLED NANOPARTICLES; CO-GLYCOLIC ACID; PHASE-II TRIAL; COMBINATION THERAPY; PLGA NANOPARTICLES; ANTICANCER DRUG; BREAST-CANCER; PACLITAXEL; 17-ALLYLAMINO-17-DEMETHOXYGELDANAMYCIN; COPOLYMER
Issue Date
201506
Publisher
ELSEVIER SCI LTD
Citation
CARBOHYDRATE POLYMERS, v.123, pp.313 - 323
Abstract
Multiple-drug combination therapy is becoming more common in the treatment of advanced cancers because this approach can decrease side effects and delay or prevent drug resistance. In the present study, we developed hyaluronic acid (HA)-decorated poly(lactic-co-glycolic acid) (PLGA) nanoparticles (HA-PLGA NPs) for co-delivery of docetaxel (DTX) and tanespimycin (17-AAG). DTX and 17-AAG were simultaneously loaded into HA-PLGA NPs using an oil-in-water emulsification/solvent evaporation method. Several formulations were tested. HA-PLGA NPs loaded with DTX and 17-AAG at a molar ratio of 2:1 produced the smallest particle size (173.3 +/- 2.2 nm), polydispersity index (0.151 +/- 0.026), and zeta potential (-12.4 +/- 0.4 mV). Approximately 60% and 40% of DTX and 17-AAG, respectively, were released over 168 h in vitro. Cytotoxicity assays performed in vitro using MCF-7, MDA-MB-231, and SCC-7 cells showed that dual drug-loaded HA-PLGA NPs at a DTX:17-AAG molar ratio of 2:1 exhibited the highest synergistic effect, with combination index values of 0.051, 0.036, and 0.032, respectively, at the median effective dose. Furthermore, synergistic antitumor activity was demonstrated in vivo in a CD44 and RHAMM (CD168) - overexpressing squamous cell carcinoma (SCC-7) xenograft in nude mice. These findings indicated that nanosystem-based co-delivery of DTX and 17-AAG could provide a promising combined therapeutic strategy for enhanced antitumor therapy. (C) 2015 Elsevier Ltd. All rights reserved.
URI
http://hdl.handle.net/YU.REPOSITORY/32085http://dx.doi.org/10.1016/j.carbpol.2015.01.064
ISSN
0144-8617
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약학대학 > 약학부 > Articles
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