A prestin-targeting peptide-guided drug delivery system rearranging concentration gradient in the inner ear: An improved strategy against hearing loss.

Eur J Pharm Sci

Guangdong 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. Electronic address:

Published: August 2023

AI Article Synopsis

  • Hearing loss is primarily caused by damage to outer hair cells in the cochlea, and local drug delivery through the round window membrane shows promise but faces challenges in effectively reaching certain cochlear regions.
  • Researchers developed poly(lactic-co-glycolic acid) nanoparticles (PLGA NPs) modified with a targeting peptide (A665) that binds to prestin, improving drug uptake in all cochlear turns.
  • The study demonstrated that curcumin-loaded A665-PLGA NPs significantly protected outer hair cells in treated guinea pigs compared to standard PLGA NPs, showing great potential for targeted therapy in treating severe hearing loss.

Article 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.

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Source
http://dx.doi.org/10.1016/j.ejps.2023.106490DOI Listing

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