Studies on Combination Chemotherapy of Doxorubicin and Cisplatin Loaded in Thermosensitive Hydrogels as Locally Controlled of Cancer Therapeutics(2/3)

Combination therapy was widely used in the clinical cancer treatments. Intravenous injection currently is the main administration route. Combination therapy could enhance efficacy and reduce the resistance of cancer cells to anti-cancer drugs by synergistic effects of different cytotoxic mechanisms. Therefore, it was widely used in the clinical cancer treatments. But intravenous injection would limit the accumulation amount of anti-cancer drugs in tumor site, and result poor tumor inhibition and systemic toxicity. In this study, we will develop a local injectable thermosensitive hydrogels with active targeting, lower systemic toxicity and preventing peritoneal adhesions for dual delivering of two anti-cancer drugs to locally treat ovarian and head and neck tumor cells. In the first year, we will prepare thermosensitive hydrogels and evaluate their physicochemical properties and drug release mechanism. The composition of hydrogel contained model drugs (cisplatin and doxorubicin), hyaluronic acid (HA) and thermosensitive polymers (for example: poloxamer and PNIPAAm). The optimal thermosensitive hydrogel formulations selected from the first year plan will be implemented in vitro/vivo studies in second and third year, respectively. We will evaluate the effects of hydrogel in inhibition of ovarian and head and neck tumor cells and reduction of systemic side effects by pharmacokinetics, pharmacodynamics and IVIS imaging system. Orthotropic ovarian and head and neck cancer animal models were established by intraperitoneal injection of SKOV3-Luciferin cells into abdominal cavity and SAS-Luciferin cells injected into buccal mucosa in mice, respectively. We will also establish the animal model with abdominal adhesion wall, and evaluate the effect of these hydrogels containing HA in preventing peritoneal adhesions. Based on this study, it is expected that therapeutic efficacy in ovarian and head and neck cancer will be enhanced with minimal systemic toxicity by designing a local injectable carrier system for two anticancer drugs in the future.