In vitro and in vivo efficacy of doxorubicin loaded biodegradable semi-interpenetrating hydrogel implants of poly (acrylic acid)/gelatin for post surgical tumor treatment.

Abstract

The paper describes the preparation and evaluation of doxorubicin loaded semi-interpenetrating polymeric hydrogel network of polyacrylic acid (PAc) and gelatin (G). Post surgical antitumor efficacy and biodistribution of doxorubicin from the implanted degradable hydrogels was investigated on Ehrlich's ascites tumor model using albino mice. Polycaprolactone diacrylate (PCL-DAr) was employed as a crosslinking agent for PAc chains whereas G was kept free. The effect of crosslinking concentration on various physico-chemical properties such as thermal behavior, swelling, degradation behavior, drug release and polymer-polymer interactions was investigated by various physico-chemical tools. Semi-interpenetrating polymeric networks (IPNs) with 0.2 mol% crosslinking concentration showed degradation within 20 days in phosphate buffer (pH 6.5). To determine the in vivo anticancer efficacy, placebo and drug laden cylindrical implants (65 ± 5 µg/implant of 10 mg) were implanted in tumor cavity post tumor excision. After predetermined time intervals (day 7, 11, 14, 20 and 25), drug biodistribution was assessed in tumor, tumor periphery, residual hydrogel and all vital organs i.e. liver, spleen, kidney, heart, lung and blood (spectrofluorimetrically). The drug distribution study showed the concentration of drug in the tumor, tumor periphery and residual hydrogel decreased with increasing time; on the 7th day, drug concentration was highest while, on the 25th day, it was negligible; however, insignificant quantities of the drug was found in vital organs. Histological examination revealed no sign of tumor recurrence until the 25th day with 100% necrosis and slight inflammation in treated the group. In vivo results established that these biodegradable implants can be utilized as post surgical therapy for solid tumors.