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.
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Authors | Sidi Yang, Yufei Chen, Kaien Gu, Alicia Dash, Casey L Sayre, Neal M Davies, Emmanuel A Ho |
Journal | International journal of nanomedicine
(Int J Nanomedicine)
Vol. 8
Pg. 2847-58
( 2013)
ISSN: 1178-2013 [Electronic] New Zealand |
PMID | 23966779
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antibodies
- CD4 Antigens
- HIV Protease Inhibitors
- Nanocapsules
- Vaginal Creams, Foams, and Jellies
- Cellulose
- hydroxyethylcellulose
- Saquinavir
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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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