Medicinal Chemistry & Computer Aided Drug Designing

Biography

Biography: Joana Marto

Abstract

Psoriasis and atopic dermatitis diseases have an excessive amount of elastase in peripheral blood neutrophils and epidermal plasminogen activator. The high levels of this enzyme inactivate the endogenous inhibitor barrier thus, the search for new human neutrophil elastase (HNE) inhibitors are required. This work presents a novel HNE inhibitor which was carried on a novel nanoparticulate system. The present study aims to develop and characterize a novel starch-based nanoparticulate carrier system (StNC) for HNE inhibitor (ER143) skin delivery The StNC were prepared by emulsion-solvent evaporation method, using Miglyol® 812 as the lipid component, Tween®80 and cetrimide as surfactants and modified starch as a polymer. The StNC was characterised in terms of particle size analysis (Malvern Mastersizer 2000 coupled with a Hydro S accessory) and the surface charge that was determined by measurements of the ζ potential (Zetasizer Nano Z in water, at 25ºC, Malvern). Permeation studies were performed using vertical Franz diffusion cells with porcine skin. Water:ethanol (70:30 w/w) were used as receptor phase for ER143. Data was expressed in cumulative amount of ER143 permeated per cm2 in order to time. Tape stripping was performed 24h after in vitro permeation studies. Stratum Corneum (SC) was separated from the epidermis and dermis using 20 tapes. An ER143 solution was used as a control. The drug content was analyzed by fluorescence methods for all of the experiments. In vivo anti-inflammatory activity was accessed using the croton oil-induced ear inflammation model in mice and StNC formulation was used as a control. The particle size obtained for StNCER143 was between 200-250 nm and showed a positive ζ potential. In vitro permeation studies thought porcine skin showed that the StNC were suitable for the delivery of ER143. After 24 h the amount of ER143 permeated was 573.2±92.7 ng/cm2 and 248.6±50.0 ng/cm2 for StNC ER143 and ER143 solution, respectively. The tape stripping assay showed that 22.7±3.9 % and 5.14±0.8 % of the drug was detected on the SC for StNC ER143 and ER143 solution, respectively, and 10.6±1.2 % and 2.2±0.5 % in epidermis and dermis for StNC ER143 and ER143 solution, respectively. Hence, StNC formulation contributed for both higher skin retention and permeation profiles of ER143possibly due to the presence of skin permeation enhancers as well as lipid content. In vivo results showed that erythema and edema were attenuated in 98% and 69% by the local application of StNC ER143 and StNC formulations, respectively, revealing a synergic effect between placebo and ER143-loaded StNC. These StNC nanocarriers are suitable for a deeper skin penetration and retention. Here we proved that starch-based nanoparticulate carrier systems (StNC) are useful as topical delivery systems, with promising in vivo results.