In vivo distribution of surface-modified PLGA nanoparticles following intravaginal delivery

摘要

Intravaginal (ivag) delivery, which is a proven way to confer local protection against STD’s contracted via the reproductive tract, is complicated by the mucus gel barrier, the hormone cycle, and the harsh mucosal environment, which leads to low residence-time for administered agents. Polymer delivery vehicles may be useful in overcoming these barriers for delivery of agents. We explored the fate of nanoparticles (NP) made from poly(lactide-co-glycolide) (PLGA) in the mouse reproductive tract after ivag delivery. The nanoparticles were modified to display avidin (Avid-NP) or 2kDa PEG (PEG-NP) on their surface. Vaginal retention fractions for both muco-adhesive Avid-NP and stealthy PEG-NP were 5x higher than unmodified PLGA particles (NP). The amount of particles associated with mucus differed across formulations (Avid-NP>NP>PEG-NP). PEG-NP was found at higher concentration in the tissue than Avid-NP and NP up to 6 hr after delivery, and particles were found within epithelial cells and the underlying submucosal stromal and fibroblast cells of the vaginal tissue. Our results demonstrate that surface properties of nanoparticles can impact their fates following ivag delivery and that PEG-modified nanoparticles are potentially useful in ivag delivery.