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.
Highlights
Injectable hydrogels have been utilized in diverse biomedical applications for a long time.[1]
Characterization of injectable carboxymethyl cellulose (CMC) and CHI formulations Based on previous work regarding hydrogel formation via electrostatic interactions,[3] as shown in Figure 1, we chose the anionic CMC and cationic CHI solutions to form an instantaneous drug depot after intratumoral injection
Each CMC and CHI solution flowed when tilted at room temperature and at 37 °C
Summary
Injectable hydrogels have been utilized in diverse biomedical applications for a long time.[1]. Various biological factors can be incorporated and quantitatively into the injectable hydrogel solution by simple stirring in the liquid state. Hydrogels are easy to handle and minimally invasive at target sites in the form of simple aqueous state injections and can replace traditional surgical procedures. Various biomaterials are the subject of ongoing research to develop injectable hydrogels.[2,3,4,5,6,7] An ionized biomaterial that bears cationic or anionic charges can exist in solution in a homogeneous state.[8] if this biomaterial solution is mixed with another that possesses an opposite charge, electrostatic interactions can result in the formation of electrostatic cross-linking between the biomaterials
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