Safety and efficacy of G2-S16 dendrimer as microbicide in healthy human vaginal tissue explants.

Background: The absence of an effective treatment and vaccine in HIV-1 pandemic place preventive strategies such as safety and effective microbicide development as a central therapeutic approach to control HIV-1 pandemic nowadays.

Results: Studies of cytotoxicity, immune population status, inflammation or tissue damage and mainly prophylactic inhibition of HIV-1 infection in vaginal human explants demonstrate the biosafety and effectivity of G2-S16 dendrimer. Human explants treated with G2-S16 dendrimer or treated and HIV-1 infected do not presented signs of irritation, inflammation, immune activation or T cell populations deregulation.

Baseline and time-updated factors in preclinical development of anionic dendrimers as successful anti-HIV-1 vaginal microbicides.

Although a wide variety of topical microbicides provide promising in vitro and in vivo efficacy, most of them failed to prevent sexual transmission of human immunodeficiency virus type 1 (HIV-1) in human clinical trials. In vitro, ex vivo, and in vivo models must be optimized, considering the knowledge acquired from unsuccessful and successful clinical trials to improve the current gaps and the preclinical development protocols. To date, dendrimers are the only nanotool that has advanced to human clinical trials as topical microbicides to prevent HIV-1 transmission.

Role of G2-S16 Polyanionic Carbosilane Dendrimer in the Prevention of Respiratory Syncytial Virus Infection In Vitro and In Vivo in Mice.

The respiratory syncytial virus (RSV) causes respiratory infection and bronchiolitis, requiring hospitalization mainly in infants. The interaction between RSV, envelope glycoproteins G and F, and cell surface heparan sulfate proteoglycans (HSPG) is required for binding and entry into the host cells. A G2-S16 polyanionic carbosilane dendrimer was identified as a possible RSV inhibitor.

Promising PEGylated cationic dendrimers for delivery of miRNAs as a possible therapy against HIV-1 infection.

Background: The appearance of resistance against new treatments and the fact that HIV-1 can infect various cell types and develop reservoirs and sanctuaries makes it necessary to develop new therapeutic approaches to overcome those failures.

Results: Studies of cytotoxicity, genotoxicity, complexes formation, stability, resistance, release and particle size distribution confirmed that G2-SN15-PEG, G3-SN31-PEG, G2-SN15-PEG-FITC and G3-SN31-PEG-FITC dendrimers can form complexes with miRNAs being biocompatible, stable and conferring protection to these nucleic acids. Confocal microscopy and flow cytometry showed effective delivery of these four dendrimers into the target cells, confirming their applicability as delivery systems.

BMS Derivatives C7-Linked to β-Cyclodextrin and Hyperbranched Polyglycerol Retain Activity against R5-HIV-1 Isolates and Can Be Deemed Potential Microbicides.

Amides from indole-3-glyoxylic acid and 4-benzoyl-2-methylpiperazine, which are related to entry inhibitors developed by Bristol-Myers Squibb (BMS), have been synthesized with aliphatic chains located at the C7 position of the indole ring. These spacers contain an azido group suitable for the well-known Cu(I)-catalyzed (3+2)-cycloaddition or an activated triple bond for the nucleophilic addition of thiols under physiological conditions. Reaction with polyols (β-cyclodextrin and hyperbranched polyglycerol) decorated with complementary click partners has afforded polyol-BMS-like conjugates that are not cytotoxic (TZM.