Nanostructured lipid carriers of alkannins and shikonins: Experimental design, characterization and bioactivity studies

Abstract

The chiral pair alkannin and shikonin and their ester derivatives (A/S), are lipophilic secondary metabolites possessing a wide spectrum of pharmacological activities. Their incorporation in lipid-based drug delivery systems can enhance their therapeutic efficacy, especially for dermal or transdermal applications. In this work, A/S in the form of oily extracts and isolated mixture of pigments from Alkanna tinctoria roots were entrapped in lipid based nanocarriers for dermal applications. In both cases, Experimental Design was carried out to evaluate the effect of process parameters on mean particle size, ζ-potential and entrapment efficiency, aiming to identify the optimum process conditions. The optimum oily extract loaded liposomes showed a mean particle size of 106 nm, ζ-potential value of −45.1 mV and entrapment efficiency (EE%) up to 72%. On the other hand, the optimum nanocarriers for the incorporation of A/S mixture showed a mean particle size of 138 nm, ζ-potential value of −15.6 mV and EE% up to 56%. The in vitro release profiles for both drug delivery systems were satisfactory and revealed that, in both cases, the release of the active pharmaceutical ingredients from the nanocarriers is controlled by diffusion. Moreover, we evaluated the effect of the optimum formulations on the viability of human dermal fibroblasts and we found that, A/S mixture loaded nanocarriers enhance cell viability. In order to assess the effect of A/S derivatives loaded nanocarriers on human fibroblasts we targeted genes related to the antioxidant cellular response, cell aging and extracellular matrix organization. The findings showed that nanocarriers induced the antioxidant response, presented a positive impact on cells’ longevity and promoted extracellular matrix organization. Based on these findings, formulated nanocarriers can be used as a potential drug delivery system for dermal applications in cosmetic products.