title: 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.
authors: Faculty of Pharmacy, University of Manitoba, Winnipeg, MB, Canada.
authors: Sidi
authors: S
authors: Yang
authors: Yufei
authors: Y
authors: Chen
authors: Kaien
authors: K
authors: Gu
authors: Alicia
authors: A
authors: Dash
authors: Casey L
authors: CL
authors: Sayre
authors: Neal M
authors: NM
authors: Davies
authors: Emmanuel A
authors: EA
authors: Ho
mesh_terms: D000906:Antibodies / Q000737:chemistry; D015704:CD4 Antigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002482:Cellulose / Q000031:analogs & derivatives; D005260:Female; D017320:HIV Protease Inhibitors / Q000737:chemistry / Q000493:pharmacokinetics* / Q000633:toxicity; D006801:Humans; D053769:Nanocapsules / Q000737:chemistry*; D019258:Saquinavir / Q000737:chemistry / Q000493:pharmacokinetics* / Q000633:toxicity; D014622:Vaginal Creams, Foams, and Jellies / Q000737:chemistry*; D014783:Viscosity
chemical_list: D000906:Antibodies; D015704:CD4 Antigens; D017320:HIV Protease Inhibitors; D053769:Nanocapsules; D014622:Vaginal Creams, Foams, and Jellies; D002482:Cellulose; C002283:hydroxyethylcellulose; D019258:Saquinavir
keywords: HIV/AIDS; antibody conjugation; intravaginal gel; microbicide; nanoparticles; saquinavir
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