Bile acid conjugated chitosan oligosaccharide nanoparticles for paclitaxel carrier

Abstract

To develop a paclitaxel carrier based on chitosan, chitosan oligosaccharide (COS) was chemically modified with bile acid (deoxycholic acid and lithocholic acid) as a hydrophobic group. Paclitaxel was loaded in bile acid conjugated chitosan oligosaccharide (CBs) nanoparticles by a dialysis method. We confirmed that the paclitaxel-loaded COS (CBs-Tx) nanoparticles could be successfully prepared with a yield of 80%–90% and paclitaxel encapsulation of 54%–70%. The size of CB nanoparticles was in the range of 200–300 nm, and it increased to 300–400 nm after paclitaxel loading with the narrow size distribution maintained. Paclitaxel-loaded CBs (CBs-Tx) nanoparticles showed remarkably high anticancer activity compared with paclitaxel in cremophore EL (CrEL)-ethanol against B16F10 cells. The antitumor efficacy in vivo was shown with significant inhibition of the tumor growth in both paclitaxel-treated groups. The effect on tumor size by the paclitaxel in the CrEL-ethanol formulation appeared to be slightly larger than that in CBs-Tx. The decrease in cytotoxicity and the increase in antitumor activity may lead to the improvement in the therapeutic index in clinical use compared to commercial paclitaxel. The efficacy of CBs-Tx nanoparticles suggests that bile acid as a hydrophobic group may have a potential application of effectively loading hydrophobic drugs such as paclitaxel.