PUBLICATION
A forskolin-loaded nanodelivery system prevents noise-induced hearing loss
- Authors
- An, X., Wang, R., Chen, E., Yang, Y., Fan, B., Li, Y., Han, B., Li, Q., Liu, Z., Han, Y., Chen, J., Zha, D.
- ID
- ZDB-PUB-220607-7
- Date
- 2022
- Source
- Journal of controlled release : official journal of the Controlled Release Society 348: 148-157 (Journal)
- Registered Authors
- Keywords
- Forskolin, Hair cells, Hearing loss, Nanoparticles, Noise exposure, Targeted delivery
- MeSH Terms
-
- Animals
- Colforsin
- Hearing Loss, Noise-Induced*/drug therapy
- Hearing Loss, Noise-Induced*/prevention & control
- Mice
- Nanoparticle Drug Delivery System
- Peptides
- Zebrafish
- PubMed
- 35659555 Full text @ J. Control Release
Citation
An, X., Wang, R., Chen, E., Yang, Y., Fan, B., Li, Y., Han, B., Li, Q., Liu, Z., Han, Y., Chen, J., Zha, D. (2022) A forskolin-loaded nanodelivery system prevents noise-induced hearing loss. Journal of controlled release : official journal of the Controlled Release Society. 348:148-157.
Abstract
Hearing loss is the most common sensory disorder worldwide and may result from age, drugs, or exposure to excessive noise. Crossing the blood-labyrinth barrier to achieve targeted drug delivery to the inner ear is key to the treatment of hearing loss. We designed a nanoparticle (NP)-based system for targeted drug delivery of forskolin (FSK) to the inner ear, driven by the prestin-targeting peptide LS19 ("ligand-receptor type interaction"). In vivo experiments in developing zebrafish embryos (4-96 h past fertilization) and mice confirmed that LS19-FSK specifically targeted and accumulated in zebrafish lateral line neuromasts and mouse outer hair cells (OHCs). LS19 peptide modification enabled LS19-FSK-NPs to rapidly target OHCs with high specificity. Furthermore, the multifunctional LS19-FSK-NPs were successfully delivered to the OHCs via the round window membrane route and exhibited slow-release properties. The sustained release and intracellular accumulation of FSK inhibited apoptosis of OHCs. Compared with LS19-NPs and FSK-NPs, LS19-FSK-NPs provided significantly stronger protection against noise-induced hearing damage, based on auditory brainstem responses at 4, 8, 16, and 32 kHz. Thus, our specially designed targeted nano-delivery system may serve as a basis for future clinical applications and treatment platforms and has the potential to significantly improve the treatment results of many inner ear diseases.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping