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Updated: Jul 27, 2025
A Comparative Study of Drug Delivery Methods Targeted to the Mouse Inner Ear: Bullostomy Versus Transtympanic Injection
Published on: March 8, 2017
A prestin-targeting peptide-guided drug delivery system rearranging concentration gradient in the inner ear: An
Xinrui Wang1, Zeming Zhou1, Chong Yu1
1Guangdong Provincial Key Laboratory of Advanced Drug Delivery & Guangdong Provincial Engineering Center of Topical Precise Drug Delivery System & Class III Laboratory of Modern Chinese Medicine Preparation & Key Laboratory of Modern Chinese Medicine of Education Department of Guangdong Province, Center for Drug Research and Development, Guangdong Pharmaceutical University, Guangzhou 510006, China.
Abstract:
Hearing loss is mainly due to outer hair cell (OHC) damage in three cochlear turns. Local administration via the round window membrane (RWM) has considerable otological clinical potential in bypassing the blood-labyrinth barrier. However, insufficient drug distribution in the apical and middle cochlear turns results in unsatisfactory efficacy. We functionalized poly (lactic-co-glycolic acid) nanoparticles (PLGA NPs) with targeting peptide A665, which specifically bound to prestin, a protein uniquely expressed in OHCs. The modification facilitated the cellular uptake and RWM permeability of NPs. Notably, the guide of A665 towards OHCs enabled more NPs perfusion in the apical and middle cochlear turns without decreasing accumulation in the basal cochlear turn. Subsequently, curcumin (CUR), an appealing anti-ototoxic drug, was encapsulated in NPs. In aminoglycoside-treated guinea pigs with the worst hearing level, CUR/A665-PLGA NPs, with superior performance to CUR/PLGA NPs, almost completely preserved the OHCs in three cochlear turns. The lack of increased low-frequencies hearing thresholds further confirmed that the delivery system with prestin affinity mediated cochlear distribution rearrangement. Good inner ear biocompatibility and little or no embryonic zebrafish toxicity were observed throughout the treatment. Overall, A665-PLGA NPs act as desirable tools with sufficient inner ear delivery for improved efficacy against severe hearing loss.
