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

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. A derivative of the spice turmeric significantly inhibits tumor growth when packaged into hydrogels that release drugs slowly. Soft, water-filled gels that can be formed by simply stirring two liquids together have attracted interest for biomedical applications including targeted delivery of drugs. Moon Suk Kim and colleagues from Ajou University in Korea now report a technique that cross-links two inexpensive natural molecules – carboxymethyl cellulose and chitosan – into a hydrogel that remains stable for weeks after injection into live mice. The team exploited this robustness to improve the bioavailability of curcumin, a promising agent against multiple types of cancer. Fluorescent labelling experiments revealed that storing curcumin microcapsules in shells made from the new hydrogel enabled dosage rates to be sustained for weeks longer than conventional treatments. Formulation of carboxymethyl cellulose (CMC) and chitosan (CHI) hydrogel containing curcumin-loaded microcapsules (Cur-M) are developed for intratumoral injection. The Cur-M-loaded CMC and CHI (CCH) formulation forms a Cur-M-loaded CCH depot after mixing via electrostatic interactions between the anionic CMC and cationic CHI. The Cur-M-loaded CCH depot lead to greater inhibition of tumor growth.