Nanostructured Lipid Carriers-Based Topical Gel of Betulinic Acid: In Vitro, In Vivo Evaluation and Dermatokinetic Analysis

The aim of this study was to improve the penetration of betulinic acid (BA) into skin efficiently by incorporating it into a nanostructured lipid carrier (NLC)-based gel. BA-NLC was prepared by the melt-emulsification and low-temperature solidification method. The optimized formulation was incorporated into the hydrogel and evaluated for pH, in vitro release, occlusion factor, and dermatokinetics. Furthermore, the transdermal penetration mechanism of the NLC gel was investigated by Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), skin histological staining, and fluorescence microscopic methods. The optimized NLC showed a particle size of 153.40 nm and a high EE of 86.21%. In vitro drug release behavior of the BA-NLC gel showed higher cumulative release at 24 h (67.17 +/- 2.39%) compared to the free drug (57.53 +/- 2.17%). In vivo dermatokinetic studies disclosed that the BA-NLC gel presented elevated C-max and AUC(0-24) in the epidermis and dermis in contrast to the conventional gel. FT-IR and DSC research indicated that the NLC formulations changed the configuration of skin keratin and augmented lipid fluidity, thus facilitating the percutaneous permeability of actives. Fluorescence microscopy also indicated improved skin penetration of the BA-NLC gel. Hence, the optimized NLC gel could potentially be a promising drug nanocarrier to boost skin drug penetration and retention.