We evaluated mechanistic insights into luteolin (LUT)-loaded elastic liposomes (OLEL1) permeated across rat skin. HSPiP software-based parameters, thermal analysis, infrared analysis, and morphological evaluations were employed to understand mechanistic observations of drug permeation and deposition. HSPiP provided HSP values (δd, δp, and δh) of OLEL1 (based on composition), LUT, excipients, and rat skin (literature value and by-default value). Rat skin was studied via Fourier transform infrared (FTIR), differential scanning calorimetry (DSC), fluorescence microscopy, scanning electron microscopy (SEM), and atomic force microscopy (AFM) studies. The δd and δh estimation of the skin and phosphatidylcholine showed close relation in terms of δd and δh. Similarly, OLEL1 and the skin might interact with each other mainly through δd and δp forces as evidenced by the predicted values. The untreated skin showed characteristic stretching and vibrations as compared to lower frequencies caused by OLEL1. DSC showed changes in the thermal behavior of the skin after OLEL1 treatment as compared to the untreated skin. Visualization of these changes was evident under fluorescence microscopy and SEM for confirmed substantial reversible surface perturbation of the skin protein layer for improved vesicle permeation and subsequent internalization with the inner skin matrix. The AFM study confirmed the nanoscale surface roughness variation caused substantially by OLEL1 and OLEL1 placebo as compared to the untreated control and drug solution. Thus, the study clearly demonstrated mechanistic insights into LUT-loaded vesicles across rat skin for enhanced permeation and drug deposition.
© 2022 The Authors. Published by American Chemical Society.