ABSTRACT
New amphiphilic carbosilane dendrons with pH-dependent behaviour based on the presence of carboxylate (propionate or succinate) groups at their peripheries and a fatty acid at the focal point were developed. In the presence of salts, they were able to form micelles with critical aggregation concentrations increasing with increasing dendron generation. Their thermodynamic parameters were calculated from surface tension measurements and their diameters at different pHs were measured by dynamic light scattering. These micelles were stable at basic pH but degraded under acidic conditions. No significant differences were found for the propionate and succinate based dendron micelles at basic or acidic pH, but the succinate dendron assemblies were more stable at neutral pH. The properties of these systems as drug nano-carriers were studied using both hydrophilic and hydrophobic molecules, and the drug loading varied with the structure and charge of the drug. In addition, due to the presence of multiple negative charges, the dendrons exhibited anti-HIV activity. Higher generation dendrons with more peripheral carboxylates that were not assembled into micelles were more active than micelles composed of lower generation dendrons having fewer peripheral carboxylates.
Subject(s)
SilanesABSTRACT
Unprotected heterosexual intercourse is the first route for sustaining the global spread of human immunodeficiency virus type 1 (HIV-1), being responsible for 80% of new HIV-1 infections in the world. The presence of inflammation in the female reproductive tract and the presence of semen increases the risk of heterosexual HIV-1 transmission. This state-of-the-art research based on an innovative nanotechnology design was focused on a toxicological study of the limitation of the activity of the novel H2O-soluble anionic carbosilane dendrimer G2-S16 in the adult cervical and foreskin epithelia. The G2-S16 dendrimer did not cause any irritation or inflammation in the vaginal epithelium, proving that this dendrimer is a safe nanocompound for vaginal application to control viral transmission. It was shown that no significant differences were found in mortality, sublethal or teratogenic effects when the zebra fish embryos were treated with G2-S16. In short, G2-S16 seems to be an ideal candidate for the development of a topical microbicide against HIV-1 infection and the next step is try in clinical trials, because of its great in vivo biocompatibility, as well as its ability to halt HIV-1 infection in the presence of semen.
