Novel biocompatible intraperitoneal drug delivery system increases tolerability and therapeutic efficacy of paclitaxel in a human ovarian cancer xenograft model

摘要: We compared the safety, toxicity, biocompatibility and anti-tumour efficacy of a novel chitosan-egg phosphatidylcholine (ePC) implantable drug delivery system that provides controlled sustained release paclitaxel (PTXePC) versus commercial formulated in Cremophor EL (PTXCrEL). Toxicity studies were conducted healthy CD-1 female mice, whereas performed SKOV-3 xenograft model ovarian cancer. Treatments consisted intraperitoneal (IP) implantation drug-free or PTXePC formulations, IP bolus PTXCrEL, (CrEL) vehicle. was assessed as number deaths, weight loss, serum hepatic enzyme levels histopathological changes. Mice implanted with formulations did not exhibit observable toxicities, local inflammation fibrous encapsulation implant. In contrast, mice receiving PTXCrEL CrEL encountered significant lethality, abnormal peritoneal organ morphology inflammation. The maximum tolerable dose (MTD) 20 mg/kg/week, PTX doses up to 280 mg/kg/week well tolerated when administered PTXePC. Enhanced achieved contrast same total 60 mg/kg PTX. formulation is safer better method for administration, increase MTD enhanced efficacy, suggesting improved therapeutic index possible clinical implications treatment tumours.