title: Vaginal microbicides and their delivery platforms.
abstract: BACKGROUND
  HIV type 1 infection, despite having fallen by one-third over the past decade, remains a global health concern affecting millions of individuals worldwide. A focal point in contemporary research aimed at global HIV prevention has been the development of safe and efficacious coitally dependent and coitally independent anti-HIV microbicides to curb heterosexual HIV transmission. Despite extensive research efforts to develop novel vaginal antiretroviral (ARV) formulations and intravaginal ring delivery systems, the clinical advancement of microbicides with improved safety, efficacy and tolerability has significantly lagged behind.
  
  
  METHODS
  This review focuses on the current status of both coitally dependent and coitally independent delivery platforms designed to increase user acceptability and clinical effectiveness of anti-HIV microbicides. The clinical failure of several vaginal microbicide candidates has propelled the field to mechanism-based ARV candidates that act more specifically on viral receptors, viral enzymes and host proteins. Consequently, improved vaginal microbicide delivery strategies that achieve uniform drug distribution with enhanced solubility, sustained drug release, improved product adherence with reduced dosing frequency and lack of effect on the vaginal mucosa and microbiota are being sought.
  
  
  CONCLUSIONS
  Clinical success with vaginal microbicides may best be achieved through the combined effects of ARV compounds that exhibit different mechanisms of action with potent activity against multidrug-resistant HIV and efficacious delivery systems.
authors: Children's Center for Cancer and Blood Diseases , Children's Hospital Los Angeles, Smith Research Tower Suite 316, 4650 Sunset Boulevard, CHLA Mailstop 160, Los Angeles, CA , USA fmuckun@chla.usc.edu.
authors: Osmond J
authors: OJ
authors: D'Cruz
authors: Fatih M
authors: FM
authors: Uckun
mesh_terms: D000282:Administration, Intravaginal; D044966:Anti-Retroviral Agents / Q000008:administration & dosage*; D002626:Chemistry, Pharmaceutical; D016503:Drug Delivery Systems; D005260:Female; D015658:HIV Infections / Q000517:prevention & control* / Q000635:transmission; D015497:HIV-1 / Q000472:pathogenicity; D006801:Humans; D015229:Sexually Transmitted Diseases, Viral / Q000517:prevention & control*
chemical_list: D044966:Anti-Retroviral Agents