Development of sulphated and naphthylsulphonated carbosilane dendrimers as topical microbicides to prevent HIV-1 sexual transmission.
OBJECTIVE
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.


METHODS
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.


CONCLUSIONS
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.
Laboratorio InmunoBiología Molecular, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain.
Enrique
E
Vacas Córdoba
Eduardo
E
Arnaiz
Miguel
M
Relloso
Carlos
C
Sánchez-Torres
Federico
F
García
Lucía
L
Pérez-Álvarez
Rafael
R
Gómez
Francisco J
FJ
de la Mata
Marjorie
M
Pion
Ma Ángeles
MÁ
Muñoz-Fernández
D000282:Administration, Intravaginal; D000287:Administration, Topical; D000818:Animals; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000494:pharmacology*; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D050091:Dendrimers / Q000008:administration & dosage / Q000494:pharmacology; D018562:Disease Transmission, Infectious / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D005260:Female; D015658:HIV Infections / Q000635:transmission*; D015497:HIV-1; D006801:Humans; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D012821:Silanes / Q000008:administration & dosage / Q000494:pharmacology; D013431:Sulfates / Q000008:administration & dosage / Q000494:pharmacology
D019380:Anti-HIV Agents; D000890:Anti-Infective Agents; D050091:Dendrimers; D012821:Silanes; D013431:Sulfates; C504072:carbosilane