An intratumoral injectable, electrostatic, cross-linkable curcumin depot and synergistic enhancement of anticancer activity

Abstract

In this study, we describe an intratumoral injectable, electrostatic, cross-linkable curcumin (Cur) drug depot to enhance anticancer activity. The key concept in this work was the preparation of an electrostatic, cross-linked carboxymethyl cellulose (CMC) and chitosan (CHI) hydrogel containing Cur-loaded microcapsules (Cur-M). The CMC and CHI solutions existed as a liquid before mixing and formed a CMC and CHI (CCH) hydrogel as a drug depot after mixing via electrostatic interactions between the anionic CMC and cationic CHI. Compared with the individual CMC and CHI solutions, the electrostatic, cross-linked CCH depot persisted in vivo for an extended period. The prepared Cur-M was easily mixed with the CMC and CHI solutions. Cur-M/CMC and Cur-;M/CHI solutions easily formed Cur-M-loaded CCH depots after simple mixing. The in vitro and in vivo Cur-M-loaded CCH depot was designed with Cur-M dispersed inside an outer shell of electrostatically cross-linked CCH. The Cur-M-loaded CCH depot produced greater inhibition of tumor growth than did Cur-M, whereas single and repeated injections of free Cur had the weakest inhibitory effects. The results of this study indicate that the electrostatic, cross-linked, Cur-M-loaded CCH depot described in this study can synergistically enhance anticancer activity in chemotherapeutic delivery systems.