Safety of G2-S16 Polyanionic Carbosilane Dendrimer as Possible HIV-1 Vaginal Microbicide

Abstract

The UNAIDS objective for 2020 was 500,000 new HIV-1 infections per year; however, the latest annual reported data confirmed 1.7 million new HIV-1 infections in that year. Those data evidences the need for new prevention strategies and prophylactic treatments. This prevention crisis occurred in spite of the knowledge and availability of efficient prevention strategies. The G2-S16 is a microbicidal polyanionic carbosilane dendrimer currently being tested for topical vaginal application, which has been shown to be efficient in the prevention of HIV-1 infection. However, safety tests were lacked. For this purpose, we injected intravenously G2-S16 dendrimer to CD1 mice, thereby analyzing the hemogram, blood biochemical markers of systemic damage, accumulation in the organs and organ-tissue damage in heart, spleen, kidney, liver and brain. This work shows that even if the G2-S16 dendrimer penetrates the epithelial tissue, it does not cause vaginal irritation or tissue damage. Moreover, the i.v. injection of the G2-S16 dendrimer did not cause a damaging effect on the studied organs and it did not modify the hemogram or the biochemical plasma markers. In conclusion, the G2-S16 dendrimer has a very good safety profile, indicating that this molecule can be a very safe and efficient vaginal microbicide.

Carbosilane dendritic nanostructures, highly versatile platforms for pharmaceutical applications

“…The application of G2‐S16‐FITC to the epithelial vaginal tissue of BALB/c mice confirmed that this family of dendrimers crosses this barrier reaching the circulatory system. The study of organs and other biochemical data confirmed that this anionic dendrimer, alone or combined with antiretroviral drugs (tenofovir and emtricitabine), is a promising system to develop an effective microbicide against HIV‐1 infection (Martin‐Moreno et al, 2022; I. Rodríguez‐Izquierdo, Sepúlveda‐Crespo, et al, 2022).…”