The improved antitumor efficacy of continuous intratumoral chemotherapy with cisplatin-loaded implants for the treatment of sarcoma 180 tumor-bearing mice

Abstract

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 tumor-bearing mice.

Local penetration of doxorubicin via intrahepatic implantation of PLGA based doxorubicin-loaded implants

“…Local chemotherapy with polymer-based drug delivery systems provides a continuous sustained release of anticancer drugs and enables high drug concentrations at the target site for a prolonged time, while reducing systemic toxicity (Gao et al., 2019). Furthermore, the targeted chemotherapy has been considered as potential future solution for both prevention and treatment of locally recurrent cancers (Mahvi et al., 2018).…”

Combination of cyanidin‐3‐O‐glucoside and cisplatin induces oxidative stress and apoptosis in HeLa cells by reducing activity of endogenous antioxidants, increasing bax/bcl‐2 mRNA expression ratio, and downregulating Nrf2 expression

“…Chemotherapeutic drugs are a suitable treatment strategy for cancer (Brezar et al., 2020). DDP is a chemotherapeutic drug which is widely used to treat various types of cancer, such as cervical cancer, head cancer, neck cancer, ovarian cancer, and non‐small‐cell lung carcinoma (Federico et al., 2020; Gao et al., 2019). Nonetheless, oxidative stress is postulated to contribute toward resistance of cancer cells to DDP (Ma et al., 2017).…”

Potential Applications of Advanced Nano/Hydrogels in Biomedicine: Static, Dynamic, Multi‐Stage, and Bioinspired

“…A cisplatin‐loaded hydrogel implant was used for treatment of sarcoma 180 tumors in mice. [ 55 ] An RGD‐modified PEG‐PAMAM‐DOX polymeric implant conjugate was used for prolonged intratumoral drug release. [ 56 ] Gels containing losartan microspheres plus (PLG‐g‐mPEG)‐cisplatin nanoparticles were used for improved drug penetration and retention, with good anti‐tumor activity.…”