Preparation, physicochemical and pharmacological study of 10-hydroxycamptothecin solid dispersion with complexation agent – xylan-nonanoic acid amphiphilic conjugates

Abstract

An amphiphilic conjugate of carboxymethyl xylan-nonanoic acid (CX-NA) was synthesized with molecular weight of 38.35 kDa, HLB value of 13.59, and critical micelle concentration of 23.17 μg/ml. CX-NA could efficiently encapsulate the model drug of 10-hydroxycamptothecin (HCPT). The drug loaded amphiphilic conjugate could self-assembled to micelles with an average diameter of 110 nm, zeta potential of −42.88 mV, and drug encapsulation efficiency of 79.8%. In vitro experiments confirmed that the drug-loaded micelles exhibited excellent stability and permeability in the intestinal environment. Transport pathway demonstrated that HCPT was uptake by cells through clathrin-mediated endocytosis. Intestinal in situ absorption study further confirmed CX-NA vehicle could enhance HPCT to transport across intestinal epithelial cells in colonic tissues. Furthermore, the formulation showed excellent anti-tumor activity in vitro and improved bioavailability of 3.4 times in vivo as comparing with free HCPT. These findings imply that this amphiphilic conjugate is a potential and promising vehicle for delivery anticancer drug.