Role of seminal plasma in the anti-HIV-1 activity of candidate microbicides

BACKGROUND: Evaluation of microbicides for prevention of HIV-1 infection in macaque models for vaginal infection has indicated that the concentrations of active compounds needed for protection by far exceed levels sufficient for complete inhibition of infection in vitro. These experiments were done in the absence of seminal plasma (SP), a vehicle for sexual transmission of the virus. To gain insight into the possible effect of SP on the performance of selected microbicides, their anti-HIV-1 activity in the presence, and absence of SP, was determined. METHODS: The inhibitory activity of compounds against the X4 virus, HIV-1 IIIB, and the R5 virus, HIV-1 BaL was determined using TZM-bl indicator cells and quantitated by measuring β-galactosidase induced by infection. The virucidal properties of cellulose acetate 1,2-benzene-dicarboxylate (CAP), the only microbicide provided in water insoluble, micronized form, in the presence of SP was measured. RESULTS: The HIV-1 inhibitory activity of the polymeric microbicides, poly(naphthalene sulfonate), cellulose sulfate, carrageenan, CAP (in soluble form) and polystyrene sulfonate, respectively, was considerably (range ≈ 4 to ≈ 73-fold) diminished in the presence of SP (33.3%). Formulations of micronized CAP, providing an acidic buffering system even in the presence of an SP volume excess, effectively inactivated HIV-1 infectivity. CONCLUSION: The data presented here suggest that the in vivo efficacy of polymeric microbicides, acting as HIV-1 entry inhibitors, might become at least partly compromised by the inevitable presence of SP. These possible disadvantages could be overcome by combining the respective polymers with acidic pH buffering systems (built-in for formulations of micronized CAP) or with other anti-HIV-1 compounds, the activity of which is not affected by SP, e.g. reverse transcriptase and zinc finger inhibitors

Block Copolymers Self-Assembly Allows Obtaining Tunable Micro or Nanoporous Membranes or Depth Filters Based on PMMA; Fabrication Method and Nanostructures

An environmentally friendly method to produce tunable bulk micro or nanoporous structures is presented. Nano and micro-porous structures are obtained by gas dissolution foaming using CO2, following the pattern of polymer blends between poly(methylmethacrylate) (PMMA) and a triblock copolymer, namely poly(methylmethacrylate)-co-poly(butyl acrylate)-co-poly(methyl methacrylate) (MAM) blends nanostructuration. Membranes or depth filters can be produced by this method, varying the amount of the triblock copolymer in the blend. Furthermore, main characteristics, such as the average pore size and porosity can be finely tuned by adjusting the process parameters (temperature or pressure) during gas foaming