A hyaluronic acid/cyclodextrin based injectable hydrogel for local doxorubicin delivery to solid tumors

Abstract

Localized delivery of anticancer drugs is often the most useful therapeutic approach for the treatment of solid tumors. The use of injectable polymeric systems that maximize drug concentration in the proximal area of the tumor represents an extremely advantageous therapeutic strategy. Here, the development of an injectable in situ forming hydrogel was accomplished by exploiting the azo-type Michael reaction between an amine derivative of hyaluronic and vinylsulfone functionalized -cyclodextrins complexing doxorubicin. This injectable system can be easily prepared and administered with timelines compatible with normal operating room procedures, as demonstrated by rheological tests. In vitro experiments revealed that the peculiar physicochemical properties of the hydrogel guarantee a sustained release of the anticancer drug that blocks the growth of colorectal carcinoma micromasses cultured in 3D conditions. In vivo studies have confirmed that the medicated hydrogel can drastically reduce the tumor mass in the animal model without causing cytotoxic side effects in other areas of the body such as the heart. Overall, the proposed system has shown promising characteristics that make it an interesting useful device for localized chemotherapy of solid tumors.