Preparation and efficacy of tumor vasculature‐targeted doxorubicin cationic liposomes coated by N‐trimethyl chitosan

Cationic liposomes (CLs) can accumulate in tumor vascular endothelial cells (VECs) to show high selective targeting ability. Therefore, chemotherapeutic agent‐loaded CLs are considered as new therapeutic vehicles to enhance the treatment efficacy. This study investigated the effect of N‐trimethyl chitosan (TMC), one of derivatives of chitosan with positive charge determined by its degree of quaternization (DQ), on preparing doxorubicin (DOX)‐loaded CLs. TMCs with various DQ, i.e., 20% (TMC20), 40% (TMC40), and 60% (TMC60) were synthesized and characterized by ¹HNMR. DOX‐loaded liposomes (DOXL) were prepared by ammonium sulfate gradients followed by TMC‐coating to obtain TMC‐coated DOXL with various positive surface charges. The morphology, size, ζ‐potential and drug release in vitro of TMC‐coated DOXL were studied compared with those of DOXL. Human umbilical vein endothelial cells (HUVECs) as cell model, the vascular targeting ability of TMC‐coated DOXL was evaluated in vitro. A solid tumor, formed by implantationmurine hepatoma cells (H₂₂) into mice, as tumor model, the tumor inhibition rate and tumor histological sections stained by HE of TMC‐coated DOXL group were researched compared with those of free DOX and DOXL group. It was found that with the increase of TMC's DQ, the positive surface charge of TMC‐coated DOXL was enhanced accordingly, which had little effect on DOX release in vitro while led to the significant increase of DOX uptake by HUVECs in vitro and the treatment effect on solid tumor in vivo. Especially, TMC‐coated DOXL showed better targeting ability to the nuclei compared with free DOX and DOXL, which could further enhance the efficacy of DOX in vivo. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011