Fabrication and characterization of andrographolide analogue (3A.1) nanosuspensions stabilized by amphiphilic chitosan derivatives for colorectal cancer therapy

Abstract

Recently, 19-tert-butyldiphenylsilyl-8,17-epoxy andrographolide (3A.1) is an andrographolide analogue which was a promising chemotherapeutic agent against some types of cancer. However, this compound has an extremely low aqueous solubility and challenging problem that limits its biological activity and clinical application. In this study, 3A.1 nanosuspensions (3A.1-NS) were fabricated by an anti-solvent technique, using three amphiphilic chitosan copolymers as surface stabilizers: naphthyl-grafted succinyl chitosan (NSC), octyl-grafted succinyl chitosan (OSC), and benzyl-grafted succinyl chitosan (BSC). Subsequently, the 3A.1-NS were freeze-dried using 5% mannitol as a cryoprotectant to transform into powder. The physicochemical characteristics demonstrated that the 3A.1-NS with optimal drug to polymer ratio of 1.5:1 had spherical morphology with mean particle size in a nanoscale (<500 nm), narrow size distribution, high negative surface charge, and high drug content. The 3A.1-NS stabilized by NSC was well dispersed in aqueous medium and this formulation was physically and chemically stable at 4 °C for at least 6 months. The in vitro cytotoxicity result showed a significant increase in the anticancer activity of the 3A.1-NS stabilized by NSC derivatives against colorectal cancer (HCT116) cells. Based on these results, the 3A.1-NS stabilized by NSC could be used as a promising delivery system for colorectal cancer treatment.