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

Abstract
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.
AuthorsSidi Yang, Yufei Chen, Kaien Gu, Alicia Dash, Casey L Sayre, Neal M Davies, Emmanuel A Ho
JournalInternational journal of nanomedicine (Int J Nanomedicine) Vol. 8 Pg. 2847-58 ( 2013) ISSN: 1178-2013 [Electronic] New Zealand
PMID23966779 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antibodies
  • CD4 Antigens
  • HIV Protease Inhibitors
  • Nanocapsules
  • Vaginal Creams, Foams, and Jellies
  • Cellulose
  • hydroxyethylcellulose
  • Saquinavir
Topics
  • Antibodies (chemistry)
  • CD4 Antigens (immunology)
  • CD4-Positive T-Lymphocytes
  • Cell Line
  • Cell Survival (drug effects)
  • Cellulose (analogs & derivatives)
  • Female
  • HIV Protease Inhibitors (chemistry, pharmacokinetics, toxicity)
  • Humans
  • Nanocapsules (chemistry)
  • Saquinavir (chemistry, pharmacokinetics, toxicity)
  • Vaginal Creams, Foams, and Jellies (chemistry)
  • Viscosity

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