Intravaginal ring delivery of tenofovir disoproxil fumarate for prevention of HIV and herpes simplex virus infection
| Autor: | Pedro M. M. Mesquita, Patrick F. Kiser, Ryan S. Teller, Rachna Rastogi, Betsy C. Herold, N. Merna Torres, Theodore J. Segarra, Ashley Huber |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Microbiology (medical)
Drug Simplexvirus food.ingredient Tenofovir media_common.quotation_subject Population Cell Culture Techniques Organophosphonates Human immunodeficiency virus (HIV) HIV Infections Pharmacology medicine.disease_cause Antiviral Agents Chemoprevention Organ Culture Techniques food immune system diseases medicine Humans Pharmacology (medical) education Original Research media_common education.field_of_study Herpes Genitalis business.industry Adenine Contraceptive Devices Female HIV virus diseases Prodrug Virology Microbicides for sexually transmitted diseases Infectious Diseases Herpes simplex virus Female business medicine.drug |
| Zdroj: | Journal of Antimicrobial Chemotherapy. 67:1730-1738 |
| ISSN: | 1460-2091 0305-7453 |
| Popis: | OBJECTIVES: A safe and effective topical prevention strategy will likely require sustained delivery of potent antiviral drugs and a delivery system that simultaneously maximizes drug distribution and overcomes the behavioural challenges related to adherence. Activity against HIV and herpes simplex virus (HSV) would be advantageous given the epidemiological link between the two pathogens. We hypothesize that tenofovir disoproxil fumarate (tenofovir DF) a prodrug of tenofovir may be more potent than tenofovir and ideal for sustained intravaginal ring (IVR) delivery. METHODS: The anti-HIV and anti-HSV activity of tenofovir and tenofovir DF were assessed in cell and explant models. Cumulative tenofovir DF release and stability from polyether urethane (PEU) ethylene-co-vinyl acetate (EVA) and silicone IVRs were compared and the activity and safety of drug released were evaluated in cervical explants and in a polarized dual-chamber model. RESULTS: Tenofovir DF inhibited HIV and HSV at approximately 100-fold lower concentrations than tenofovir and retained activity in the presence of semen. PEU rings delivered >1 mg/day of tenofovir DF for 30 days. Pre-treatment of cervical explants with 10 mug/mL tenofovir DF or eluants from PEU minirings resulted in >90% inhibition of HIV and reduced HSV-2 yields by 2.5 log. Tenofovir DF and eluants did not prevent cell growth or polarization or have any deleterious effects on an epithelial barrier. CONCLUSIONS: The findings support the development of a PEU tenofovir DF ring which may provide potent and sustained protection against HIV and HSV. |
| Databáze: | OpenAIRE |
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