Grun Molly K, Honhar Praveen, Wang Yazhe, Rossano Samantha, Khang Minsoo, Suh Hee Won, Fowles Krista, Kliman Harvey J, Cavaliere Alessandra, Carson Richard E, Marquez-Nostra Bernadette, Saltzman W Mark
Department of Chemical & Environmental Engineering Yale University New Haven Connecticut USA.
Department of Biomedical Engineering Yale University New Haven Connecticut USA.
Bioeng Transl Med. 2024 May 9;9(5):e10661. doi: 10.1002/btm2.10661. eCollection 2024 Sep.
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 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.
长效阴道剂型可以提高阴道杀菌剂的治疗效果，但实现向阴道管的长期给药一直是一项重大挑战。为了增进对阴道剂型滞留和生物分布的了解，我们描述了一种在非人类灵长类动物中使用锆标记的生物粘附纳米颗粒（BNP）进行无创成像的方法。我们还检查了重复应用BNP的安全性。食蟹猴经阴道给药的BNP在24小时（滞留率1.7%）和120小时（滞留率0.1%）后仍可检测到。BNP未转移至子宫或进入体循环。对阴道液和血浆中炎症生物标志物的分析表明，即使多次给药，BNP也是安全且具有生物相容性的。BNP是一种很有前景的阴道给药治疗载体。使用此处开发的非人类灵长类动物成像材料和方法进行的进一步研究可能有助于推进BNP和其他长效阴道剂型的临床转化。
