Merck
  • Home
  • Search Results
  • 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

Millipore
Bifido Selective Supplement B, suitable for microbiology
Supelco
5α-Androstan-17β-ol-3-one, VETRANAL®, analytical standard
Sigma-Aldrich
Magnesium chloride, suitable for insect cell culture, BioReagent, ≥97.0%
Sigma-Aldrich
Magnesium chloride, anhydrous, ≥98%
Sigma-Aldrich
Urea, meets USP testing specifications
Sigma-Aldrich
Urea, ReagentPlus®, ≥99.5%, pellets
Sigma-Aldrich
Urea, puriss., meets analytical specification of Ph. Eur., BP, USP, 99.0-100.5%, 99.0-101.0% (calc. on dry substance)
Sigma-Aldrich
Magnesium chloride, powder, <200 μm
Sigma-Aldrich
5α-Androstan-17β-ol-3-one, purum, ≥99.0% (TLC)
Sigma-Aldrich
Urea, puriss. p.a., ACS reagent, reag. Ph. Eur., ≥99%
Sigma-Aldrich
DL-Lactic acid, ~90% (T)
Sigma-Aldrich
Urea, BioUltra, for molecular biology, ≥99% (T)
Sigma-Aldrich
Methyl 4-hydroxybenzoate, tested according to Ph. Eur.
Sigma-Aldrich
Methyl 4-hydroxybenzoate, ≥99%, FCC
Sigma-Aldrich
Magnesium chloride, AnhydroBeads, −10 mesh, 99.9% trace metals basis
Sigma-Aldrich
Methyl 4-hydroxybenzoate, BioXtra, ≥99.0% (titration)
Sigma-Aldrich
Methyl 4-hydroxybenzoate, BioReagent, suitable for insect cell culture
Sigma-Aldrich
Methyl 4-hydroxybenzoate, analytical standard
Sigma-Aldrich
Methyl 4-hydroxybenzoate, ReagentPlus®, ≥99.0%, crystalline
Sigma-Aldrich
DL-Lactic acid, 85 % (w/w), syrup
Sigma-Aldrich
Urea, powder, BioReagent, for molecular biology, suitable for cell culture
Sigma-Aldrich
Urea, ACS reagent, 99.0-100.5%
Sigma-Aldrich
Urea, suitable for electrophoresis
Sigma-Aldrich
Urea, BioXtra, pH 7.5-9.5 (20 °C, 5 M in H2O)
Sigma-Aldrich
Lactic acid solution, ACS reagent, ≥85%
Sigma-Aldrich
Magnesium chloride, AnhydroBeads, −10 mesh, 99.99% trace metals basis
Sigma-Aldrich
Urea, ReagentPlus®, ≥99.5%
USP
Urea, United States Pharmacopeia (USP) Reference Standard
Urea, European Pharmacopoeia (EP) Reference Standard
Supelco
Urea, 8 M (after reconstitution with 16 mL high purity water)