PURPOSE: To assess the potential of polymeric nanoparticles (NPs) to affect the 
genital distribution and local and systemic pharmacokinetics (PK) of the 
anti-HIV microbicide drug candidate dapivirine after vaginal delivery.
METHODS: Dapivirine-loaded, poly(ethylene oxide)-coated 
poly(epsilon-caprolactone) (PEO-PCL) NPs were prepared by a nanoprecipitation 
method. Genital distribution of NPs and their ability to modify the PK of 
dapivirine up to 24 h was assessed after vaginal instillation in a female mouse 
model. Also, the safety of NPs upon daily administration for 14 days was 
assessed by histological analysis and chemokine/cytokine content in vaginal 
lavages.
RESULTS: PEO-PCL NPs (180-200 nm) were rapidly eliminated after administration 
but able to distribute throughout the vagina and lower uterus, and capable of 
tackling mucus and penetrate the epithelial lining. Nanocarriers modified the PK 
of dapivirine, with higher drug levels being recovered from vaginal lavages and 
vaginal/lower uterine tissues as compared to a drug suspension. Systemic drug 
exposure was reduced when NPs were used. Also, NPs were shown safe upon 
administration for 14 days.
CONCLUSIONS: Dapivirine-loaded PEO-PCL NPs were able to provide likely favorable 
genital drug levels, thus attesting the potential value of using this vaginal 
drug delivery nanosystem in the context of HIV prophylaxis.