Development of sulphated and naphthylsulphonated carbosilane dendrimers as topical microbicides to prevent HIV-1 sexual transmission
| Autor: | Marjorie Pion, Federico García, Ma Ángeles Muñoz-Fernández, Lucía Pérez-Álvarez, Eduardo Arnáiz, Francisco Javier de la Mata, Rafael Gómez, Miguel Relloso, Enrique Vacas Córdoba, Carlos Sánchez-Torres |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Male
Dendrimers Sexual transmission Anti-HIV Agents Administration Topical Immunology CD1 HIV Infections Peripheral blood mononuclear cell Proinflammatory cytokine Mice Anti-Infective Agents Microbicide Disease Transmission Infectious medicine Animals Humans Immunology and Allergy Mice Inbred ICR Dose-Response Relationship Drug Sulfates business.industry Transmission (medicine) Silanes Microbicides for sexually transmitted diseases Administration Intravaginal Infectious Diseases medicine.anatomical_structure HIV-1 Vagina Female business |
| Zdroj: | AIDS. 27:1219-1229 |
| ISSN: | 0269-9370 |
| DOI: | 10.1097/qad.0b013e32835f2b7a |
| Popis: | OBJECTIVES For the last 20 years, the idea of alternative prevention strategies based on the use of topical vaginally products to inhibit HIV-1 infection in women has been established. The concept of a 'microbicide' product has been born out of the unavailability of a vaccine against HIV-1 and the problems of women in negotiating the use of preventive prophylaxis by their partners, especially in developing countries. DESIGN We have developed and evaluated polyanionic carbosilane dendrimers G3-S16 and G2-NF16 with sulphated and naphthylsulphonated end groups as nonspecific microbicides. METHODS Cellular in-vitro or in-vivo models were used to evaluate the safety, biocompatibility and anti-HIV ability of two polyanionic carbosilane dendrimers. RESULTS Both dendrimers showed high biosafety in human epithelial cell lines derived from uterus and vagina and in primary blood human cells (PBMC). These dendrimers not only have a partial capacity to block the entry of different X4 and R5 HIV-1 isolates inside epithelial cells but protect the epithelial monolayer from cell disruption and also reduce HIV-1 infection of activated PBMC. Additionally, treatment of epithelial cells with G3-S16 or G2-NF16 dendrimers did not produce changes in proinflammatory cytokines profile, in proliferation of PBMC, on microbiota or sperm survival. Finally, no irritation or vaginal lesions were detected in female CD1(ICR) mice after dendrimers vaginal administration. CONCLUSION These interesting results suggest that G3-S16 or G2-NF16 could be effective to inhibit HIV infection and transmission within genital mucosa as well as the spread of HIV transmission to human PBMC. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|