順式-二氨二氯合鉑 (cis-Diamineplatinu (Ⅱ) dichloride, CDDP) 為目前最常見的化學治療藥物，主要被應用在治療如頭頸癌、泌尿道癌以及肺癌等其他類型癌症。雖然 CDDP 在臨床的運用上十分廣泛，然而其本身的副作用反造成臨床醫師在治療病患上面臨諸多困難，最為顯著已知副作用包括：耳毒性、腎毒性、神經毒性以及噁心嘔吐等。在本研究中主要，設計可包覆 CDDP 於白蛋白超音波微氣泡對比劑 (Microbubbles, MBs)，一種穩定且可承載足夠劑量抗癌藥物之新型白蛋白超音波微氣泡對比劑，並結合超音波產生的穴蝕效應打開細胞膜通透度，增加腫瘤內局部的藥物累積濃度，抑制下咽癌癌細胞生長，減少周圍組織的傷害及副作用。
CDDP-MBs 透過動態光散射粒徑分析儀量測粒徑及庫爾特計數器分析濃度等實驗，並分別進行細胞實驗 (n=5) 與動物活體實驗 (n=7) 其實驗組別分為 (1)控制組 (C)；(2) 單純白蛋白微氣泡對比劑 (MBs)；(3) CDDP溶液 (CDDP)；(4) CDDP溶液混合MBs (CDDP+MBs)；(5) CDDP包覆於MBs (CDDP-MBs)；(6) CDDP混合 MBs 結合超音波 (CDDP+MBs+US)； (7) CDDP 包覆於 MBs 結合超音波 (CDDP-MBs+US)。
本研究以不同濃度之白蛋白溶液與 1.2 mg/ml CDDP 所配製而成的 CDDP-MBs，其粒徑大小隨白蛋白濃度132 mg/ml、140 mg/ml、150 mg/ml的增加而改變，故粒徑大小依序為 1.70 ± 0.73、2.42 ± 0.61、2.44 ± 4.49 µm；其中以白蛋白濃度 140 mg/ml包覆 CDDP 所製成的微氣泡對比劑數目含量最高；包覆效率達 10.09 ±
0.23 %；在體外試驗中，未經超音波施打前，CDDP-MBs 組對下咽癌細胞毒性效果不佳，但經超音波施打後整體毒殺能力大幅提升，平均細胞存活率下降 26 % (p<0.001)；在動物試驗中，可觀察到 CDDP-MBs+US 與 CDDP 治療趨勢結果相似，但 MBs 包覆 CDDP 時可使其副作用減低，從腎臟病理切片結果觀察到 CDDO+MBs+US 比CDDP-MBs+US有較嚴重的損傷，故綜合以上 CDDP-MBs 其治療的效果能降低 CDDP 所引起的副作用。

Cisplatin (cis-Diamineplatinu (Ⅱ) dichloride, CDDP) is one of the most frequently used agents in the treatment a variety of tumor, particularity head and neck, genitourinary, and lung cancer. Although CDDP was widely used in clinical, the side effects (Ototoxicity, Nephrotoxicity, Neurotoxicity, Nausea and Vomiting) limit the dose of cisplatin that can be safely administered.
The aim of this study is to establish a new, stable, high drug-loading capacity albumin-shelled microbubbles (MBs) combined with ultrasound (US) to enhance hypopharyngeal cancer treatment. The CDDP-MBs combined with ultrasound can increased the capillary permeability through cavitation mechanism. It increased the local concentrations of tumor site, inhibited the hypopharyngeal cancer cell growth without causing surrounding normal tissues damage and reduced the side effects.
The size distribution and concentration of the CDDP-loaded MBs in suspension were measured by DLS and Coulter Counter respectively. The in vitro (n=6) and in vivo (n=7) experimental parameters will be divided into eight groups: (1) no treatment (Control); (2) microbubbles (MBs) alone; (3) cisplatin solution (CDDP) alone; (4) CDDP solution mixed with MBs (CDDP+MBs); (5) CDDP-loaded MBs (CDDP-MBs) alone; (6) US combined with penetrating CDDP (CDDP+US); (7) US combined with MBs and penetrating CDDP (CDDP+MBs+US); (8) US combined with CDDP-MBs (CDDP-MBs+US).
In our research, the CDDP-MBs prepared with different concentrations of albumin solution (132 mg/ml, 140 mg/ml and 150 mg/ml) and 1.2 mg/ml CDDP solution. The mean diameters of CDDP-MBs with various concentrations of albumin were 1.70 ± 0.73, 2.42 ± 0.61, 2.44 ± 4.49 µm respectively. The maximum loading efficiency of CDDP on MBs (with 140 mg/ml albumin : 1.2 mg/ml CDDP) was 10.09 ± 0.23 %. In the in vitro study, CDDP-MBs can increase 26 % cell toxicity after ultrasound irradiation (p<0.001). In small animal treatment, the treatment efficacies in CDDP-MBs+US and CDDP groups were similar before 17 days. Instead of CDDP, it can be expected that CDDP-loaded microbubbles reduces the side effect more significant.

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