Bruno Sarmento
Universidade do Porto, Portugal
Title: Nanoparticles-in-vaginal films for combined delivery of anti-HIV microbicide drugs
Biography
Biography: Bruno Sarmento
Abstract
There is an urgent need to reinforce battle against HIV/AIDS, namely by investing more in preventing new infections. Scientific and medical evidence produced over recent years supports that both oral and topical pre-exposure prophylaxis (PrEP) are promising approaches that can reduce sexual transmission of the virus. Still, anti-retroviral with different physicochemical properties may be challenging to combine in one single microbicide product We propose a new system comprising the incorporation of nanoparticles (NPs) into films for the combined vaginal delivery of hydrophobic/hydrophilic molecules. EFV-loaded poly (lactic-co-glycolic acid) NPs were incorporated alongside free TFV into fast disintegrating films during film manufacturing. The delivery system was characterized for physicochemical properties, as well as for genital distribution, local and systemic 24 h pharmacokinetics, and safety upon intra vaginal administration to mice. EFV NPs with diameter of 145 nm were incorporated into a film with TFV. The film was soft and flexible. Disintegration time in simulated vaginal fluid was 9 min, resulting in dispersions with osmolality values near physiologic and pH of 4.24±0.02. The film presented low toxicity to CaSki, HEC-1-A and HeLa cells. NPs were evenly distributed and retained upon vaginal administration to mice. Mild epithelial penetration of NPs was observed. Drug concentrations in vaginal lavages and tissues peaked rapidly after film administration but slowly decreased up to 24 h. Still, drug concentrations were maintained at potentially protective levels. Films were found safe after daily 14 days administration as assessed by histological observation and analysis of IL-1b, IL-6, KC and TNFα levels.