Summary: | 碩士 === 國立臺灣科技大學 === 醫學工程研究所 === 104 === Cisplatin (cis-diaminedichloroplatinum) is one of the most frequently used antineoplastic agents. It is usually administered i.v., in combination with other antineoplastic agents. Nephrotoxicity is the major side effect that limits the dose of cisplatin that can be safely administered. Other commonly observed toxicities that may lead to dose reduction are peripheral neuropathy, ototoxicity, myelosuppression, and hypersensitivity reactions or even nausea and vomiting. For this reason, research in the past was aimed at the development of new platinum compounds with less systemic side effects. In this study, ultrasound (US) mediated release of cisplatin loaded microbubbles (MBs), increased local concentrations, reduced the dose and side effects was investigated.
The experimental parameters were randomly divided into seven groups : (1) control (2) MBs alone (MBs) (3) cisplatin loaded MBs (C-MBs) (4) MBs mixed with cisplatin (MBs+C) (5) US combined with MBs (MBs+US) (6) US combined with cisplatin loaded MBs (C-MBs+US) (7) US combined with MBs mixed with cisplatin (MBs+C+US) .
In the experimental aspect, the maximum loading efficiency of cisplatin in MBs (with albumin:cisplatin=1:5) was 25.61% (n=5). Scanning electron microscopy images of the MBs and C-MBs with various compositions, respectively. In cytotoxicity experiments, the cell survival in US combined with C-MBs group (62±0.046%) is more significant lower than MBs+C (82±0.02%) (P <0.05). In animal experiments, the tumor growth rates in the control group, C-MBs, cisplatin, MBs +C+US C-MBs+US were 61.89±2.10、28.33±3.35、15.89±1.43、11.24±2.04和12.91±1.94%. In histopathological results, liver and kidney injury was observed in MBs+C combination of US and cisplatin alone groups. The treatment area in tumor tissue is not uniform in MBs+C combination of US and cisplatin alone group and is uniform in C-MBs combined with US. Overall, the combination of cisplatin loaded MBs and US is a promising approach for treating colon cancer.
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