Preparation and in vitro and in vivo Study of Asiaticoside-Loaded Nanoemulsions and Nanoemulsions-Based Gels for Transdermal Delivery

PURPOSE: Asiaticoside (ASI), a compound of triterpene pentacyclic saponins, has apparently therapeutic efficacy on human hypertrophic scar. However, the characteristics of large molecular weight, low water solubility and poor lipophilicity do not favor the diffusion through the stratum corneum (SC). Therefore, it is expected that the development of a transdermally delivered formulation may enhance the permeability ratio (Qn) of ASI for its clinical application. In this study, we designed asiaticoside-loaded nanoemulsions (ASI-NEs) and nanoemulsions-based gels (ASI-NBGs) and studied their mechanism for transdermal delivery. METHODS: The preparation of ASI-NEs was optimized by simplex lattice design (SLD). The ex vivo transdermal penetration and the in vivo pharmacokinetics studies were studied, respectively. The skin irritation of ASI-NEs and ASI-NBGs was measured on normal and damaged skin in rabbits, and the transcutaneous mechanisms of ASI-NEs and ASI-NBGs were determined by HE stained and confocal laser scanning microscopy (CLSM). RESULTS: The mean particle size of ASI-NEs was 132±5.84nm. The ex vivo skin permeation study verified that the Qn of the optimized ASI-NEs and ASI-NBGs was about 13.65 times and 5.05 times higher than that of the ordinary ASI-G group. In vivo, the pharmacokinetics studies showed that ASI-NEs and ASI-NBGs reached the peak value in the skin quickly and maintained stable release for a long time with high bioavailability. ASI-NEs and ASI-NBGs were proved to be safe when applied for topical skin usage, and they could play a therapeutic role through the skin mainly by acting on the microstructure of the SC and by means of the skin adnexal pathways. CONCLUSION: ASI-NEs and ASI-NBGs were effectively developed to overcome the barrier properties of the skin and show high drug penetration through the transdermal route. In addition, we found that ASI-NEs and ASI-NBGs are safe when applied through transdermal delivery system.