Skip to Content
Merck
  • Prophylactic treatment with a novel bioadhesive gel formulation containing aciclovir and tenofovir protects from HSV-2 infection.

Prophylactic treatment with a novel bioadhesive gel formulation containing aciclovir and tenofovir protects from HSV-2 infection.

The Journal of antimicrobial chemotherapy (2014-08-21)
Gita N Shankar, Carsten Alt
ABSTRACT

Over-the-counter access to an inexpensive, effective topical microbicide could reduce the transmission of HIV and would increase women's control over their health and eliminate the need to obtain their partners' consent for prophylaxis. Chronic infection with herpes simplex virus 2 (HSV-2), also known as human herpes virus 2, has been shown to facilitate HIV infection and speed the progression to immunodeficiency disease. Our objective is to develop a drug formulation that protects against both HSV-2 and HIV infection and adheres to the vaginal surface with extended residence time. We developed a formulation using two approved antiviral active pharmaceutical ingredients, aciclovir and tenofovir, in a novel bioadhesive vaginal delivery platform (designated SR-2P) composed of two polymers, poloxamer 407 NF (Pluronic(®) F-127) and polycarbophil USP (Noveon(®) AA-1). The efficacy of the formulation to protect from HSV-2 infection was tested in vitro and in vivo. In addition to its efficacy, it is essential for a successful microbicide to be non-irritating to the vaginal mucosa. We therefore tested our SR-2P platform gel in the FDA gold-standard microbicide safety model in rabbits and also in a rat vaginal irritation model. Our studies indicated that SR-2P containing 1% aciclovir and 5% tenofovir protects (i) Vero cells from HSV-2 infection in vitro and (ii) mice from HSV-2 infection in vivo. Our results further demonstrated that SR-2P was not irritating in either vaginal irritation model. We conclude that SR-2P containing aciclovir and tenofovir may be a suitable candidate microbicide to protect humans from vaginal HSV-2 infection.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Potassium chloride, AnhydroBeads, −10 mesh, 99.999% trace metals basis
Pricing and availability is not currently available. Contact Technical Service
Sigma-Aldrich
Potassium chloride, BioUltra, for molecular biology, ≥99.5% (AT)
Pricing and availability is not currently available. Contact Technical Service
Sigma-Aldrich
Urea solution, BioUltra, ~8 M in H2O
Pricing and availability is not currently available. Contact Technical Service
Supelco
Acetic acid, analytical standard
Pricing and availability is not currently available. Contact Technical Service
Sigma-Aldrich
Potassium chloride, tested according to Ph. Eur.
Pricing and availability is not currently available. Contact Technical Service
Supelco
Potassium chloride solution, conductance standard C acc. to ISO 7888, 0.001 M KCl
Pricing and availability is not currently available. Contact Technical Service
Supelco
Potassium chloride solution, BioUltra, ~3 M in H2O
Pricing and availability is not currently available. Contact Technical Service
Supelco
Potassium chloride solution, conductance standard B acc. to ISO 7888, 0.01 M KCl
Pricing and availability is not currently available. Contact Technical Service
Sigma-Aldrich
Acetic acid-12C2, 99.9 atom % 12C
Pricing and availability is not currently available. Contact Technical Service
Supelco
Methyl Paraben, PESTANAL®, analytical standard
Pricing and availability is not currently available. Contact Technical Service
Sigma-Aldrich
Potassium chloride, 99.999% trace metals basis
Pricing and availability is not currently available. Contact Technical Service
Sigma-Aldrich
Acetic acid, natural, ≥99.5%, FG
Pricing and availability is not currently available. Contact Technical Service
Sigma-Aldrich
Lactic acid, natural, ≥85%
Pricing and availability is not currently available. Contact Technical Service
Sigma-Aldrich
HEPES, BioUltra, for molecular biology, ≥99.5% (T)
Pricing and availability is not currently available. Contact Technical Service
Sigma-Aldrich
Acetic acid, for luminescence, BioUltra, ≥99.5% (GC)
Pricing and availability is not currently available. Contact Technical Service
Sigma-Aldrich
Potassium chloride solution, BioUltra, for molecular biology, ~1 M in H2O
Pricing and availability is not currently available. Contact Technical Service
Sigma-Aldrich
D-(−)-Fructose, BioUltra, ≥99.0% (HPLC)
Pricing and availability is not currently available. Contact Technical Service
Millipore
D-(−)-Fructose, ≥99.0% (HPLC), suitable for microbiology
Pricing and availability is not currently available. Contact Technical Service
Sigma-Aldrich
D-(−)-Fructose, tested according to Ph. Eur.
Pricing and availability is not currently available. Contact Technical Service
Sigma-Aldrich
Citrate Concentrated Solution, BioUltra, for molecular biology, 1 M in H2O
Pricing and availability is not currently available. Contact Technical Service
Supelco
Potassium chloride solution, for Ag/AgCl electrodes, ~3 M KCl, saturated with silver chloride
Pricing and availability is not currently available. Contact Technical Service
Sigma-Aldrich
Lactic acid, 85%, FCC
Pricing and availability is not currently available. Contact Technical Service
Sigma-Aldrich
Urea-12C, 99.9 atom % 12C
Pricing and availability is not currently available. Contact Technical Service
Sigma-Aldrich
Acetic acid, ≥99.5%, FCC, FG
Pricing and availability is not currently available. Contact Technical Service
Sigma-Aldrich
Potassium chloride, ≥99.99% trace metals basis
Pricing and availability is not currently available. Contact Technical Service
Sigma-Aldrich
Magnesium chloride solution, for molecular biology, 1.00 M±0.01 M
Pricing and availability is not currently available. Contact Technical Service
Sigma-Aldrich
Lactic acid, meets USP testing specifications
Pricing and availability is not currently available. Contact Technical Service
Sigma-Aldrich
Potassium chloride, powder, BioReagent, suitable for cell culture, suitable for insect cell culture, ≥99.0%
Pricing and availability is not currently available. Contact Technical Service
Sigma-Aldrich
Potassium chloride, BioXtra, ≥99.0%
Pricing and availability is not currently available. Contact Technical Service
Sigma-Aldrich
Potassium chloride solution, 0.075 M, sterile-filtered, BioXtra, suitable for cell culture
Pricing and availability is not currently available. Contact Technical Service