Pilot PET study of vaginally administered bioadhesive nanoparticles in cynomolgus monkeys: Kinetics and safety evaluation.

Autor: Grun MK; Department of Chemical & Environmental Engineering Yale University New Haven Connecticut USA., Honhar P; Department of Biomedical Engineering Yale University New Haven Connecticut USA., Wang Y; Department of Biomedical Engineering Yale University New Haven Connecticut USA., Rossano S; Department of Biomedical Engineering Yale University New Haven Connecticut USA., Khang M; Department of Biomedical Engineering Yale University New Haven Connecticut USA., Suh HW; Department of Biomedical Engineering Yale University New Haven Connecticut USA., Fowles K; Department of Radiology & Biomedical Imaging Yale School of Medicine New Haven Connecticut USA., Kliman HJ; Department of Obstetrics, Gynecology & Reproductive Sciences Yale School of Medicine New Haven Connecticut USA., Cavaliere A; Department of Radiology & Biomedical Imaging Yale School of Medicine New Haven Connecticut USA., Carson RE; Department of Biomedical Engineering Yale University New Haven Connecticut USA.; Department of Radiology & Biomedical Imaging Yale School of Medicine New Haven Connecticut USA., Marquez-Nostra B; Department of Radiology, Division of Advanced Medical Imaging Research University of Alabama at Birmingham Birmingham Alabama USA., Saltzman WM; Department of Chemical & Environmental Engineering Yale University New Haven Connecticut USA.; Department of Biomedical Engineering Yale University New Haven Connecticut USA.; Department of Cellular & Molecular Physiology Yale School of Medicine New Haven Connecticut USA.; Department of Dermatology Yale School of Medicine New Haven Connecticut USA.
Jazyk: angličtina
Zdroj: Bioengineering & translational medicine [Bioeng Transl Med] 2024 May 09; Vol. 9 (5), pp. e10661. Date of Electronic Publication: 2024 May 09 (Print Publication: 2024).
DOI: 10.1002/btm2.10661
Abstrakt: Long-lasting vaginal dosage forms could improve the therapeutic efficacy of vaginal microbicides, but achieving long-term delivery to the vaginal canal has been a significant challenge. To advance understanding of vaginal dosage retention and biodistribution, we describe a method of noninvasive imaging with 89 Zr-labeled bioadhesive nanoparticles (BNPs) in non-human primates. We additionally examined the safety of repeated BNP application. BNPs administered vaginally to cynomolgus monkeys were still detected after 24 h (1.7% retention) and 120 h (0.1% retention). BNPs did not translocate to the uterus or into systemic circulation. Analysis of inflammatory biomarkers in the vaginal fluid and plasma suggest that BNPs are safe and biocompatible, even after multiple doses. BNPs are a promising delivery vehicle for vaginally administered therapeutics. Further studies using the non-human primate imaging materials and methods developed here could help advance clinical translation of BNPs and other long-lasting vaginal dosage forms.
Competing Interests: YW, MK, HWS, and WMS are inventors on patent applications related to bioadhesive PLA‐HPG nanoparticles. WMS is a founder and consultant to Stradefy Biosciences, which is developing bioadhesive nanoparticles for other applications.
(© 2024 The Authors. Bioengineering & Translational Medicine published by Wiley Periodicals LLC on behalf of American Institute of Chemical Engineers.)
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje