title: Nanomedicine strategy for optimizing delivery to outer hair cells by surface-modified poly(lactic/glycolic acid) nanoparticles with hydrophilic molecules.
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.
authors.affiliation: School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, People’s Republic of China|Guangdong Provincial Key Laboratory of Advanced Drug Delivery, Guangdong Pharmaceutical University, Guangzhou, People’s Republic of China
authors.forename: Xingxing
authors.initials: X
authors.lastname: Wen
authors.affiliation: School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, People’s Republic of China|Guangdong Provincial Key Laboratory of Advanced Drug Delivery, Guangdong Pharmaceutical University, Guangzhou, People’s Republic of China
authors.forename: Shan
authors.initials: S
authors.lastname: Ding
authors.affiliation: School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, People’s Republic of China|Guangdong Provincial Key Laboratory of Advanced Drug Delivery, Guangdong Pharmaceutical University, Guangzhou, People’s Republic of China
authors.forename: Hui
authors.initials: H
authors.lastname: Cai
authors.affiliation: School of Public Health, Guangdong Pharmaceutical University, Guangzhou, People’s Republic of China
authors.forename: Junyi
authors.initials: J
authors.lastname: Wang
authors.affiliation: School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, People’s Republic of China
authors.forename: Lu
authors.initials: L
authors.lastname: Wen
authors.affiliation: School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, People’s Republic of China|Guangdong Provincial Key Laboratory of Advanced Drug Delivery, Guangdong Pharmaceutical University, Guangzhou, People’s Republic of China
authors.forename: Fan
authors.initials: F
authors.lastname: Yang
authors.affiliation: School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, People’s Republic of China|Guangdong Provincial Key Laboratory of Advanced Drug Delivery, Guangdong Pharmaceutical University, Guangzhou, People’s Republic of China
authors.forename: Gang
authors.initials: G
authors.lastname: Chen
mesh_terms: D000818:Animals; D002460:Cell Line; D048271:Chitosan / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry* / Q000493:pharmacokinetics; D005260:Female; D006168:Guinea Pigs; D018072:Hair Cells, Auditory, Outer / Q000378:metabolism*; D057927:Hydrophobic and Hydrophilic Interactions; D019344:Lactic Acid / Q000737:chemistry*; D008297:Male; D008422:Materials Testing; D050997:Nanomedicine; D053758:Nanoparticles / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D014018:Tissue Distribution
chemical_list: D004337:Drug Carriers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011092:Polyethylene Glycols; D048271:Chitosan
keywords: HEI-OC1 cell; PLGA nanoparticles; cochlea; inner ear drug delivery; surface chemistry