Mucus-penetrating nanoparticles for vaginal drug delivery protect against herpes simplex virus

Laura M. Ensign, Benjamin C. Tang, Ying Ying Wang, Terence A. Tse, Timothy Hoen, Richard Cone, Justin Hanes

Research output: Contribution to journalArticle

Abstract

Incomplete coverage and short duration of action limit the effectiveness of vaginally administered drugs, including microbicides, for preventing sexually transmitted infections. We investigated vaginal distribution, retention, and safety of nanoparticles with surfaces modified to enhance transport through mucus. We show that mucus-penetrating particles (MPPs) provide uniform distribution over the vaginal epithelium, whereas conventional nanoparticles (CPs) that are mucoadhesive are aggregated by mouse vaginal mucus, leading to poor distribution. Moreover, when delivered hypotonically, MPPs were transported advectively (versus diffusively) through mucus deep into vaginal folds (rugae) within minutes. By penetrating into the deepest mucus layers, more MPPs were retained in the vaginal tract after 6 hours compared to CPs. After 24 hours, when delivered in a conventional vaginal gel, patches of a model drug remained on the vaginal epithelium, whereas the epithelium was coated with drug delivered by MPPs. We then developed MPPs composed of acyclovir monophosphate (ACVp). When administered before vaginal herpes simplex virus 2 challenge, ACVp-MPPs protected 53% of mice compared to only 16% protected by soluble drug. Overall, MPPs improved vaginal drug distribution and retention, provided more effective protection against vaginal viral challenge than soluble drug, and were nontoxic when administered daily for 1 week.

Original languageEnglish (US)
Article number138ra79
JournalScience translational medicine
Volume4
Issue number138
DOIs
StatePublished - Jun 13 2012

ASJC Scopus subject areas

  • Medicine(all)

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