Abstract
BackgroundCopper has antimicrobial properties and has been studied for its activity against viruses, including HIV. Copper complexed within a phthalocyanine ring, forming copper (II) phthalocyanine sulfate (CuPcS), may have a role in microbicide development when used intravaginally.MethodsCuPcS toxicity was tested against cervical epithelial cells, TZM-BL cells, peripheral blood mononuclear cells (PBMC), and cervical explant tissues using cell viability assays. In vivo toxicity was assessed following intravaginal administration of CuPcS in female BALB/C mice and measured using a standardized histology grading system on reproductive tract tissues. Efficacy studies for preventing infection with HIV in the presence of various non-toxic concentrations of CuPcS were carried out in TZM-BL, PBMC, and cervical explant cultures using HIV-1BAL and various pseudovirus subtypes. Non-linear regression was applied to the data to determine the EC50/90 and CC50/90.ResultsCuPcS demonstrated inhibition of HIV infection in PBMCs at concentrations that were non-toxic in cervical epithelial cells and PBMCs with EC50 values of approximately 50 μg/mL. Reproductive tract tissue analysis revealed no toxicity at 100 mg/mL. Human cervical explant tissues challenged with HIV in the presence of CuPcS also revealed a dose–response effect at preventing HIV infection at non-toxic concentrations with an EC50 value of 65 μg/mL.ConclusionThese results suggest that CuPcS may be useful as a topical microbicide in concentrations that can be achieved in the female genital tract.Electronic supplementary materialThe online version of this article (doi:10.1186/s12985-015-0358-5) contains supplementary material, which is available to authorized users.
Highlights
Copper has antimicrobial properties and has been studied for its activity against viruses, including HIV
Nontoxic concentrations of CuPcS were determined by exposing ME-180, TZM-BL, and peripheral blood mononuclear cells (PBMC) cell lines to various concentrations of the compound
In this study we demonstrate that CuPcS has activity against HIV-1 in the range of concentrations that are nontoxic to cervical epithelial cells, PBMCs, and cervical explant tissues
Summary
Copper has antimicrobial properties and has been studied for its activity against viruses, including HIV. Copper complexed within a phthalocyanine ring, forming copper (II) phthalocyanine sulfate (CuPcS), may have a role in microbicide development when used intravaginally. Most copper-induced insults to cells are the result of free radical damage to biomolecules [7], which can be countered by eukaryotic cells through mechanisms that sequester, expel, or inactivate the copper ions or efficiently repair the damage [12]. Free copper ions diffusing throughout the vagina have the potential to produce reactive species that could damage the integrity of the vaginal epithelial cell barrier by overwhelming cell repair mechanisms or by interfering with protective microflora [5]. Copper ions complexed within larger molecules such as sulfonated phthalocyanines (CuPcS) might prevent the production of such reactive species while precluding absorption across the epithelial barrier and intracellular penetration
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