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首页> 外文期刊>Colloids and Surfaces, B. Biointerfaces >pH-sensitive polymeric cisplatin-ion complex with styrene-maleic acid copolymer exhibits tumor-selective drug delivery and antitumor activity as a result of the enhanced permeability and retention effect
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pH-sensitive polymeric cisplatin-ion complex with styrene-maleic acid copolymer exhibits tumor-selective drug delivery and antitumor activity as a result of the enhanced permeability and retention effect

机译：pH敏感的聚合物顺铂离子与苯乙烯-马来酸共聚物的复合物由于增强的通透性和保留效果而具有肿瘤选择性的药物递送和抗肿瘤活性

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Cisplatin (CDDP) is widely used to treat various cancers. However, its distribution to normal tissues causes serious adverse effects. For this study, we synthesized a complex of styrene-maleic acid copolymer (SMA) and CDDP (SMA-CDDP), which formed polymeric micelles, to achieve tumor-selective drug delivery based on the enhanced permeability and retention (EPR) effect. SMA-CDDP is obtained by regulating the pH of the reaction solution of SMA and CDDP. The mean SMA-CDDP particle size was 102.5 nm in PBS according to electrophoretic light scattering, and the CDDP content was 20.1% (w/w). The release rate of free CDDP derivatives from the SMA-CDDP complex at physiological pH was quite slow (0.75%/day), whereas it was much faster at pH 5.5 (4.4%/day). SMA-CDDP thus had weaker in vitro toxicity at pH 7.4 but higher cytotoxicity at pH 5.5. In vivo pharmacokinetic studies showed a 5-fold higher tumor concentration of SMA-CDDP than of free CDDP. SMA-CDDP had more effective antitumor potential but lower toxicity than did free CDDP in mice after i.v. administration. Administration of parental free CDDP at 4 mg/kg x 3 caused a weight loss of more than 5%; SMA-CDDP at 60 mg/kg (CDDP equivalent) x 3 caused no significant weight change but markedly suppressed S-180 tumor growth. These findings together suggested using micelles of the SMA-CDDP complex as a cancer chemotherapeutic agent because of beneficial properties-tumor-selective accumulation and relatively rapid drug release at the acidic pH of the tumor-which resulted in superior antitumor effects and fewer side effects compared with free CDDP. (C) 2015 Elsevier B.V. All rights reserved.
机译：顺铂（CDDP）被广泛用于治疗各种癌症。但是，其分布到正常组织会引起严重的不良反应。对于本研究，我们合成了苯乙烯-马来酸共聚物（SMA）和CDDP（SMA-CDDP）的复合物，形成了聚合物胶束，从而基于增强的渗透性和保留（EPR）效果实现了肿瘤选择性药物的递送。 SMA-CDDP是通过调节SMA与CDDP反应溶液的pH值而获得的。根据电泳光散射，在PBS中的平均SMA-CDDP粒径为102.5nm，并且CDDP含量为20.1％（w / w）。 SMA-CDDP复合物中游离CDDP衍生物在生理pH值下的释放速度非常慢（0.75％/天），而在pH 5.5（4.4％/天）下则快得多。因此，SMA-CDDP在pH 7.4下的体外毒性较弱，但在pH 5.5下的细胞毒性较高。体内药代动力学研究表明，SMA-CDDP的肿瘤浓度比游离CDDP高5倍。静脉内注射后，SMA-CDDP比游离CDDP具有更有效的抗肿瘤潜力，但毒性更低。行政。以4 mg / kg x 3的剂量服用无父母的CDDP可使体重减轻5％以上; SMA-CDDP的剂量为60 mg / kg（相当于CDDP）x 3时，体重无明显变化，但明显抑制了S-180肿瘤的生长。这些发现共同表明，将SMA-CDDP复合物的胶束用作癌症化学治疗剂是因为其具有有益的特性-肿瘤选择性积累和在肿瘤的酸性pH处相对较快的药物释放-与之相比，具有更好的抗肿瘤作用和较少的副作用免费的CDDP。 （C）2015 Elsevier B.V.保留所有权利。

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