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Nanomedicine strategy for optimizing delivery to outer hair cells by surface-modified poly(lactic/glycolic acid) nanoparticles with hydrophilic molecules

Authors Wen X, Ding S, Cai H, Wang J, Wen L, Yang F, Chen G

Received 19 July 2016

Accepted for publication 22 September 2016

Published 10 November 2016 Volume 2016:11 Pages 5959—5969


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Linlin Sun

Video abstract presented by Wen et al.

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Xingxing Wen,1,2 Shan Ding,1,2 Hui Cai,1,2 Junyi Wang,3 Lu Wen,1 Fan Yang,1,2 Gang Chen1,2

1School of Pharmacy, 2Guangdong Provincial Key Laboratory of Advanced Drug Delivery, 3School of Public Health, Guangdong Pharmaceutical University, Guangzhou, People’s Republic of China

Abstract: Targeted drug delivery to outer hair cells (OHCs) in the cochlea by nanomedicine strategies forms an effective therapeutic approach for treating hearing loss. Surface chemistry plays a deciding role in nanoparticle (NP) biodistribution, but its influence on such distribution in the cochlea remains largely unknown. Herein, we report the first systematic comparison of poly(lactic/glycolic acid) nanoparticles (PLGA NPs) with or without surface modification of hydrophilic molecules for optimizing the delivery to OHCs both in vitro and in vivo. NPs that were surface modified with poloxamer 407 (P407), chitosan, or methoxy poly(ethylene glycol) and the unmodified NPs were highly biocompatible with L929 and House Ear Institute-organ of Corti 1 cells as well as cochlear tissues. Interestingly, among all the examined NPs, P407-PLGA NPs showed the greatest cellular uptake and prominent fluorescence in cochlear imaging. More importantly, we provide novel evidence that the surface-modified NPs reached the organ of Corti and were transported into the OHCs at a higher level. Together, these observations suggest that surface modification with hydrophilic molecules will allow future clinical applications of PLGA NPs, especially P407-PLGA NPs, in efficient hearing loss therapy.

Keywords: inner ear drug delivery, PLGA nanoparticles, surface chemistry, cochlea, HEI-OC1 cell

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