Intra-peritoneal administration of paclitaxel with non-animal stabilized hyaluronic acid as a vehicle – A new strategy against peritoneal dissemination of gastric cancer

Abstract

Background and aim: Intra-peritoneal administration (i.p.) of Taxanes has recently been reported to be effective for the treatment of peritoneal dissemination, presumably because extremely high concentration of the drug is achievable onto the disseminated nodules as compared to intra-venous administration. Here, we aimed to investigate the ability of non-animal stabilized hyaluronic acid (NASHA) to retain the anti-cancer drugs in the peritoneal cavity, and, consequently, improve the efficacy of i.p. administration of paclitaxel. Methods: Mice were inoculated i.p. with MKN45P gastric cancer cells. The mice received i.p. administrations of paclitaxel, without or with NASHA, once a week for 3 consecutive weeks, and the intra-peritoneal nodules were counted after 4 weeks. The ability of NASHA to retain the i.p. administered liquid and paclitaxel in abdominal cavity was also investigated. Finally, the concentration of paclitaxel in metastatic nodule was measured with HPLC. Results: In the group receiving paclitaxel with NASHA, the number of disseminated nodules were significantly smaller than in those receiving paclitaxel without NASHA. The fluid volumes and concentration of paclitaxel recovered from the abdominal cavity as well as the concentrations of paclitaxel in metastatic nodule were significantly increased by the addition of NASHA. Conclusion: Our results indicate that NASHA improves the exposure time of i.p. administrated paclitaxel to disseminated nodules by retaining the drug in the abdominal cavity. Since the material is used in cosmetic surgery with few adverse effects, NASHA can be clinically used as the vehicle for the i.p. administration of anti-cancer agents for advanced gastric cancer with peritoneal dissemination.