Exploring palmitoylated arabinogalactan in solid lipid nanoparticles: formulation design and in vitro assessment for hepatospecific targeting

Abstract

The present study evaluates the feasibility of the incorporation of palmitoylated arabinogalactan in solid lipid nanoparticles and its potential as a hepatospecific targeting ligand. Human hepatocellular carcinoma (HCC) is a neoplasm presenting low survival and higher incidence, due to difficulties in the treatment modalities to effectively place cancer therapeutics at the site. Targeting asialoglycoprotein receptors on the surface of hepatocytes employing lipid nanoparticles, and liposomes presents opportunities for improvement in therapy. The objective of the present investigation was to fabricate and evaluate the potential of palmitoylated arabinogalactan (PAG) incorporated SLNs to target asialoglycoprotein receptors. Daunorubicin-loaded targeted SLNs prepared by ultrasound dispersion method were evaluated for in vitro release and in vitro cytotoxicity. Lipids, surfactants, and biocompatible solvents were screened for SLN formation and optimization was done using 22 factorial designs. The particle size for formulations was below 200 nm with a unimodal distribution. Differential scanning calorimetry analysis revealed the interaction of lipids with other components characterized by a shift in lipid melting endotherm. Daunorubicin-loaded PAG SLNs released a significantly higher amount of daunorubicin at pH 5.5 as compared to pH 7.4, providing an advantage for targeted tumor therapy. In vitro cytotoxicity studies showed that daunorubicin depicted a dose-dependent reduction in viability in all cell lines treated with formulation as well as free drug. SLNs showed enhancement in intracellular uptake of daunorubicin thereby establishing their potential in improved treatment of HCC and warrant further in vivo investigations. -