Galactose‐grafted chylomicron‐mimicking emulsion: evaluation of specificity against HepG‐2 and MCF‐7 cell lines

Objectives A chylomicron‐mimicking lipid emulsion was prepared and loaded with paclitaxel (paclitaxel‐CM) and was further grafted with galactose (paclitaxel‐GCM) using palmitoyl‐galactosamine, which was synthesized by reacting galactosamine hydrochloride with N ‐hydroxy succinimide ester of palmitic acid. Palmitoyl‐galactosamine was used as a ligand for asialoglycoprotein receptors. Methods The uptake characteristics of the emulsions were evaluated in HepG‐2 cells (human hepatocarcinaoma), which express asialoglycoprotein receptors, and MCF‐7 (breast cancer) cells, which are devoid of these receptors. Key findings The incorporation efficiency of paclitaxel‐CM was 68.05 ± 4.80% and that of paclitaxel‐GCM was 72.10 ± 3.93% when the emulsion was prepared with 7.5% (w/w) paclitaxel/lipid phase. The globule size of paclitaxel‐GCM and paclitaxel‐CM was 124 ± 8.67 and 96.45 ± 5.78 nm, respectively. The release of paclitaxel from both of the formulations was fairly sustained: 50 ± 3.2% of paclitaxel in 24 h. The cytotoxicity and uptake of paclitaxel‐GCM were significantly higher ( P < 0.05) in HepG‐2 cells than MCF‐7 cells, while for paclitaxel‐CM cytotoxicity and uptake were similar in the two cell lines. This study clearly demonstrates that upon surface modification palmitoyl‐galactosamine remains an integral part of the formulation. Paclitaxel solubility can be improved using optimum paclitaxel/lipid phase ratios. The paclitaxel‐GCM formulation recognizes asialoglycoprotein receptors over‐expressed on HepG‐2 cells. Conclusions Under our experimental conditions, the proposed paclitaxel‐GCM formulation is an ideal delivery vehicle for specific targeting to liver cancer cells, which is anticipated to result in improved efficacy and reduced toxicity to normal cells.