Preparation Of Polylactic Acid-based Sustained-release Cisplatin Implant And Its Antitumor Efficacy In 180 Sarcoma Mouse Models

Cancer is the leading cause of death worldwide in the 21 st century.According to the GLOBOCAN 2018 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer(IARC),there are an estimated 18.1 million new cancer cases and 9.6 million cancer deaths in 2018.Though progress in cancer therapy has significantly reduced cancer incidence and improved survival,cancer is still a major public health problem and the leading cause of death in China.The conventional systemic chemotherapy is the most commonly used methods of cancer therapy.However,intravenously administered anticancer drugs must overcome transport barriers before reaching the cancer site.As a result,only a small fraction of drugs could be transported into the tumor,higher systemic doses result in undesirable side effects to normal tissues.Local chemotherapy with polymer-based drug delivery systems has been considered as an very promising method to improve treatment and minimize systemic side effects.Moreover,local chemotherapy is highlighted as potential future solution for both prevention and treatment of locally recurrent cancers.Cisplatin is the most commonly used antitumor drug in the chemotherapy of a variety of malignancies.However,the severe side effects and drug resistance limit its clinical application.The aim of this study was to develop PLGA-based cisplatin-loaded implants and evaluate the antitumor efficacy of continuous intratumoral chemotherapy with the implants.The cisplatin-loaded implants were prepared by the direct compression method and characterized regarding drug content,micromorphology,in vitro and in vivo drug release profiles.Furthermore,the antitumor activity of the implants was conducted in sarcoma 180 tumor-bearing mice.The SEM images showed smooth surface of the implants and the mean drug content of the tested implants was(37.7% ± 0.5%,w/w).Both in vitro and in vivo release profiles of the implants were characterized by initial burst release followed by the sustained-release of cisplatin.Intratumoral implantation of the cisplatin-loaded implants could effectively inhibit the tumor growth.Additionally,intratumoral chemotherapy with the implants significantly reduced the systemic toxicity compared with intravenous injection of cisplatin.It is worth noting that an increase in the dose of the implants led to a higher tumor suppression rate without additional systemic toxicity.These results demonstrated that cisplatin-loaded implants enhanced the antitumor efficacy and reduced the dose-related side effects in sarcoma 180 tumorbearing mice.