Intravaginal (ivag) delivery, which is a proven way to confer local protection against STDs contracted via the reproductive tract, is complicated by the mucus gel barrier, the hormone cycle, and the harsh mucosal environment that leads to low residence-time for administered agents. Polymer delivery vehicles may be useful in overcoming these barriers. In this study, 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 2 kDa PEG (PEG–NP) on their surface. Vaginal retention fractions for both muco-adhesive Avid–NP and stealthy PEG–NP were 5× 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 h after delivery, and particles were found within epithelial cells, 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. Moreover, we show that the muco-evasive PEG-modified nanoparticles are the most effective among the delivery vehicles tested for this application.Graphical abstract
PLGA nanoparticles with surface coatings of PEG and carrying fluorescent Coumarin-6 dye efficiently avoided leakage after vaginal delivery, traversed through the mucus gel layer, and were efficiently taken up by the tissues of the mouse female reproductive tract. On average, PEG-modified nanoparticle formulations displayed higher tissue retention across all measured time points than unmodified or Avidin-modified PLGA nanoparticles. *Denotes statistical significance with p < 0.042; † denotes p < 0.053.