Abstract 3232: Anticancer drug delivery utilizing a mucoadhesive hybrid gel for local regional gynecologic applications

Abstract

Abstract Cervical cancer is one of the leading gynecological malignancies affecting women worldwide. Although surgical cytoreduction and systemic chemotherapy combined with radiation are standard therapies, accessibility to such treatment as well as nonspecific toxicity limit its efficacy. We hypothesize that the site-specific local application of anticancer drugs utilizing innovative delivery technologies will improve efficacy, reduce toxicity and provide cost-effective, accessible therapeutic options. To test this hypothesis, we developed a mucoadhesive, polymeric hybrid chitosan gel embedding drug containing alginate beads. An optimized gel was achieved by mixing 1% chitosan (w/v) with glycerol dissolved in acetic acid (AA) solution at a volume ratio of 1:2 or 1:3 (2% AA:glycerol). Alginate beads were formed by dropping alginate solution (2%, w/v) into various concentrations of CaCl2 solution. In testing swelling properties, dried alginate beads transforming into wet ones were capable of releasing the drug load. Beads obtained from 1% CaCl2 solution demonstrated optimal and stable swelling properties that were 40 times greater than other formulations. Such beads, loaded with cisplatin (CDDP) dissolved in 0.9% NaCl were prepared. The loaded CDDP concentration was confirmed by colorimetric assay with Sn2Cl2 after re-swelling of the dried beads. Drug loaded-beads contained an average of 0.2mg of CDDP per 10 mg of dried beads. There was a linear correlation (R2 = 0.92) between the swelling ratio of the alginate beads and the amount of CDDP released, allowing the ability to estimate CDDP concentration based on the swelling ratio. Drug-loaded dried alginate beads were placed into a chitosan solution resulting in a hybrid hydrogel. To test the feasibility of local application of the gel on a mucosal surface, we investigated the swelling and mucoadhesive properties on a 4cm2 section of mouse peritoneal sidewall. We confirmed the complete swelling of beads within the hybrid gel suggested sufficient release of CDDP from the beads onto a biological surface. Mucoadhesive properties and toxicity were evaluated in vivo by surgically placing a 1cm2 sized gel pellet into the left peritoneal sidewall of immune competent female mice. The hybrid gel remained in place for 72 hours exhibiting no signs of local inflammation, tissue damage or systemic toxicity. Our results strongly suggest the feasibility of application of this hybrid gel to various mucosal surfaces. Ongoing experiments will evaluate the efficacy and safety of our hybrid gel/CDDP as a radiation enhancer in the treatment of cervical cancer and for the treatment of cervical dysplasia. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3232. doi:10.1158/1538-7445.AM2011-3232