Department of Radiology, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu City, Shiga 520-2192, Japan.
Eur J Radiol. 2009 Dec;72(3):534-40. doi: 10.1016/j.ejrad.2008.07.030. Epub 2008 Sep 7.
To confirm prolonged cisplatin release from drug-loaded gelatin microspheres (GMSs) and their improved chemoembolic anti-cancer effect against VX2 liver tumors in rabbits.
Two groups of twelve rabbits each were treated intraarterially either with 2 mg/kg cisplatin-loaded GMSs (=0.04 mg/kg cisplatin) or 0.04 mg/kg cisplatin solution by administering them into the right renal artery. Platinum concentrations within the renal parenchyma were analyzed immediately following infusion (day 0) and on days 1, 3, and 7 using the atomic absorption method. In a second experiment four groups of five rabbits each with implanted VX2 liver tumors were treated intraarterially through the hepatic artery with the following drugs: 2 mg/kg cisplatin-loaded GMSs (=0.04 mg/kg cisplatin) (group I), 2 mg/kg GMSs without any drug (group II), 1.5 mg/kg cisplatin solution (group III) and saline (group IV). Tumor volumes were analyzed pre-injection and 7 days after with MRI allowing calculating the relative tumor growth rate (%). Degree of liver cell necrosis was assessed on the histopathological specimens.
The renal parenchymal platinum concentrations (microg/ml) with 4.51+/-2.25 (day 0), 1.59+/-0.70 (day 1), 0.72+/-0.10 (day 3) and 0.20+/-0.06 (day 7) were significantly more pronounced after cisplatin-loaded GMS on days one and three compared to cisplatin with 1.99+/-0.55, 0.08+/-0.03, 0.18+/-0.01 and 0.10+/-0.07, respectively. Relative tumor growth rates resulted in 84.5%+/-26.4 (group I); 241.4%+/-145.1 (II); 331.9%+/-72.2 (III), and 413.6%+/-103.6 (IV) with statistical significant differences between groups I and III, and groups I and IV. Similar degrees of necrosis were observed in both GMSs treated groups, while ballooning of hepatocytes was highest in cisplatin-loaded GMSs.
With cisplatin-loaded GMSs more pronounced and prolonged local parenchymal cisplatin concentrations may be achieved offering the advantage of an increased and prolonged anti-cancer effect compared to cisplatin alone or controls. Moreover this proves indirectly the breakdown and release of cisplatin from the GMSs which is of primary importance for drug delivery systems.
证实负载顺铂的明胶微球（GMSs）能长时间释放顺铂，并提高其对兔 VX2 肝肿瘤的化学栓塞抗癌作用。
两组各 12 只兔分别经右肾动脉内给予 2mg/kg 负载顺铂的 GMSs（=0.04mg/kg 顺铂）或 0.04mg/kg 顺铂溶液。在输注后即刻（第 0 天）及第 1、3 和 7 天，采用原子吸收法分析肾实质内的铂浓度。在第二项实验中，每组 5 只植入 VX2 肝肿瘤的兔经肝动脉内分别给予以下药物：2mg/kg 负载顺铂的 GMSs（=0.04mg/kg 顺铂）（I 组）、2mg/kg 不含任何药物的 GMSs（II 组）、1.5mg/kg 顺铂溶液（III 组）和生理盐水（IV 组）。在注射前和 7 天后进行 MRI 分析肿瘤体积，计算相对肿瘤生长率（%）。评估肝组织学标本中的肝细胞坏死程度。
负载顺铂 GMSs 在第 1 天和第 3 天的肾实质铂浓度（μg/ml）分别为 4.51+/-2.25（第 0 天）、1.59+/-0.70（第 1 天）、0.72+/-0.10（第 3 天）和 0.20+/-0.06（第 7 天），明显高于顺铂 1.99+/-0.55、0.08+/-0.03、0.18+/-0.01 和 0.10+/-0.07。相对肿瘤生长率分别为 84.5%+/-26.4（I 组）；241.4%+/-145.1（II 组）；331.9%+/-72.2（III 组）和 413.6%+/-103.6（IV 组），I 组和 III 组以及 I 组和 IV 组之间的差异有统计学意义。在 GMSs 治疗组中观察到相似程度的坏死，而负载顺铂的 GMSs 中肝细胞气球样变性最严重。
负载顺铂的 GMSs 可实现更显著和更持久的局部实质内顺铂浓度，与单独使用顺铂或对照组相比，提供了增加和延长抗癌作用的优势。此外，这间接证明了 GMSs 中顺铂的分解和释放，这对药物传递系统至关重要。
