Synthesis, characterization, and in vitro evaluation of palmitoylated arabinogalactan with potential for liver targeting

Arabinogalactan (AG), a water soluble polysaccharide with more than 80 mol % galactose units, was hydrophobized by covalent attachment of palmitoyl chains using a base-catalyzed esterification reaction with the objective of effective amalgamation of arabinogalactan in liposomes for targeting asialoglycoprotein receptors (ASGPR) on liver parenchymal cells. Palmitoylated AG (PAG) was characterized by physico-chemical parameters, IR, 1H NMR, and 13C NMR and molecular weight determination by gel permeation chromatography. PAG was incorporated in liposomes and the liposomes were characterized by dynamic light scattering, optical microscopy, zeta potential, and transmission electron microscopic (TEM) techniques. The liposomal system was evaluated for acute toxicity in swiss albino mice and was found to be safe. Targeting ability of PAG was confirmed by in vitro binding affinity to Ricinus communis agglutinin (RCA120), a lectin specific for galactose. The liposomal system with PAG was evaluated for cytotoxicity on HepG2, MCF7, and A549 cancer cell lines. Cytotoxicity study revealed enhanced activity on ASGPR-expressive HepG2 cells as compared to MCF7.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Arabinogalactan, asialoglycoprotein receptor specific polysaccharide, was hydrophobically modified using palmitoyl chloride. ► The safety profile of the targeting ligand, hydrophobic derivative of arabinogalactan, was established in vivo. ► The receptor binding ability of the targeting ligand (palmitoylated arabinogalactan) was established by agglutination study. ► A liposomal delivery system modified with the targeting ligand was successfully fabricated and characterized.