Design and Development of Biotinylated SNEDDS for Improved Efficacy of Curcumin against Hepatocellular Carcinoma

Abstract

Curcumin (CUR) exhibits significant efficacy against various cancers, including hepatocellular carcinoma (HCC). However, its limited oral bioavailability greatly restricts clinical applications. Lipid-based nanocarriers offer a promising strategy to enhance both the anticancer potential and oral bioavailability of lipophilic drugs. In this study, we have formulated a biotinylated CUR SNEDDS to target it more efficiently to tumor cells that overexpress biotin receptors, such as those found in HCC. This targeted delivery system aims to enhance the therapeutic efficacy of CUR while minimizing systemic toxicity, offering a more effective treatment strategy for HCC. For this purpose, the components of the formulation were determined based on their solubility as well as their capacity to emulsify. A ternary phase diagram was constructed for the components selected for the formulation to optimize the concentrations of the constituents. The developed SNEDDS were evaluated for thermodynamic stability, physicochemical properties, drug-excipient interactions, in vitro dissolution, and hepatoprotective activities. Histopathological analysis and gene expression data showed that the biotinylated CUR-SNEDDS exhibited therapeutic potential in an in vivo HCC model, reducing inflammation, fibrosis, and cancer nodules. The enhanced hepatoprotective activity of biotinylated SNEDDS can be attributed to the nanosized formulation, which solubilizes CUR, prolongs its half-life, and facilitates preferential accumulation at the biotin receptor, which is overexpressed in HCC. These findings highlight the potential of biotinylated SNEDDS as an effective therapeutic strategy for enhancing the efficacy and targeting of CUR in HCC treatment.

Graphical Abstract