Biodistribution and pharmacokinetics of dapivirine-loaded nanoparticles after vaginal delivery in mice.
OBJECTIVE
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.
IINFACTS - Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde, Instituto Superior de Ciências da Saúde-Norte, CESPU, Rua Central de Gandra, 1317, 4585-116, Gandra, Portugal, j.dasneves@gmail.com.
José
J
das Neves
Francisca
F
Araújo
Fernanda
F
Andrade
Mansoor
M
Amiji
Maria Fernanda
MF
Bahia
Bruno
B
Sarmento
D000282:Administration, Intravaginal; D000818:Animals; D005260:Female; D015658:HIV Infections / Q000188:drug therapy; D054303:HIV Reverse Transcriptase / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051379:Mice; D053758:Nanoparticles / Q000032:analysis / Q000378:metabolism*; D011091:Polyesters / Q000032:analysis / Q000378:metabolism*; D011743:Pyrimidines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D014018:Tissue Distribution; D014621:Vagina / Q000378:metabolism*
D011091:Polyesters; D011743:Pyrimidines; C458722:polyethylene oxide-polycaprolactone copolymer; D054303:HIV Reverse Transcriptase; C481671:Dapivirine