Novel intravaginal nanomedicine for the targeted delivery of saquinavir to CD4+ immune cells

Int J Nanomedicine. 2013:8:2847-58. doi: 10.2147/IJN.S46958. Epub 2013 Aug 8.


The goal of this study was to develop and characterize an intravaginal nanomedicine for the active targeted delivery of saquinavir (SQV) to CD4(+) immune cells as a potential strategy to prevent or reduce HIV infection. The nanomedicine was formulated into a vaginal gel to provide ease in self-administration and to enhance retention within the vaginal tract. SQV-encapsulated nanoparticles (SQV-NPs) were prepared from poly(lactic-co-glycolic acid) (PLGA) and conjugated to antihuman anti-CD4 antibody. Antibody-conjugated SQV-NPs (Ab-SQV-NPs) had an encapsulation efficiency (EE%) of 74.4% + 3.7% and an antibody conjugation efficiency (ACE%) of 80.95% + 1.10%. Over 50% of total loaded SQV was released from NPs over 3 days. NPs were rapidly taken up by Sup-T1 cells, with more than a twofold increase in the intracellular levels of SQV when delivered by Ab-SQV-NPs in comparison to controls 1 hour post-treatment. No cytotoxicity was observed when vaginal epithelial cells were treated for 24 hours with drug-free Ab-NPs (1,000 μg/mL), 1% HEC placebo gel (200 mg/mL), or 1% HEC gel loaded with drug-free Ab-NPs (5 mg NPs/g gel, 200 mg/mL of gel mixture). Overall, we described an intravaginal nanomedicine that is nontoxic and can specifically deliver SQV into CD4(+) immune cells. This platform may demonstrate potential utility in its application as postexposure prophylaxis for the treatment or reduction of HIV infection, but further studies are required.

Keywords: HIV/AIDS; antibody conjugation; intravaginal gel; microbicide; nanoparticles; saquinavir.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies / chemistry
  • CD4 Antigens / immunology
  • CD4-Positive T-Lymphocytes
  • Cell Line
  • Cell Survival / drug effects
  • Cellulose / analogs & derivatives
  • Female
  • HIV Protease Inhibitors / chemistry
  • HIV Protease Inhibitors / pharmacokinetics*
  • HIV Protease Inhibitors / toxicity
  • Humans
  • Nanocapsules / chemistry*
  • Saquinavir / chemistry
  • Saquinavir / pharmacokinetics*
  • Saquinavir / toxicity
  • Vaginal Creams, Foams, and Jellies / chemistry*
  • Viscosity


  • Antibodies
  • CD4 Antigens
  • HIV Protease Inhibitors
  • Nanocapsules
  • Vaginal Creams, Foams, and Jellies
  • Cellulose
  • hydroxyethylcellulose
  • Saquinavir