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紫杉醇支架膜在小鼠皮下肿瘤异种移植下植入后,在肿瘤组织中呈现出紫杉醇的极度积累,并具有优异的抗肿瘤功效。

A stent film of paclitaxel presenting extreme accumulation of paclitaxel in tumor tissue and excellent antitumor efficacy after implantation beneath the subcutaneous tumor xenograft in mice.

机构信息

School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China.

School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China.

出版信息

Int J Pharm. 2018 Dec 20;553(1-2):29-36. doi: 10.1016/j.ijpharm.2018.09.060. Epub 2018 Sep 26.

Abstract

Anti-tumor drug/stent combinations play a dual role of stent and local chemotherapy to cancer. Herein, a series of paclitaxel (PTX) loaded polylactic acid (PLA) stent films were studied on drug release characteristics and in vivo antitumor effects. The film was implanted beneath and released drug towards the subcutaneous PC-3 tumor xenograft in mice, which consisted of a PTX-loaded layer and a drug-free backing layer. The concentrations of PTX were 10-10 times higher than those in normal 20 tissue or organs in 26 days after implantation of the 50% PTX/20% PEG-loaded film, indicating an extreme accumulation of PTX in tumor tissue. The tumor volumes kept unchanged for the initial 10 days after implantation of the PTX-loaded films and then increased slightly, implying tumor growth was remarkably inhibited. Moreover, the results showed that the drug release can be effectively modulated by addition of PEG in the drug-loaded layer, present an unidirectional way by adding a backing layer, and the drug films could arrest PC-3 prostate cancer cells in G2/M phase and induce apoptosis after 300 days of drug release. With the advantages of prolonged drug release and long-term effectiveness, the films have great potential for anti-tumor treatment by local administration.

摘要

抗肿瘤药物/支架组合在癌症中发挥支架和局部化疗的双重作用。在此,研究了一系列载紫杉醇(PTX)的聚乳酸(PLA)支架膜的药物释放特性和体内抗肿瘤作用。该膜被植入到皮下 PC-3 肿瘤异种移植物下方,并向其释放药物,支架膜由载药层和无药背衬层组成。在植入载有 50%PTX/20%PEG 的膜后 26 天,PTX 的浓度比正常 20 组织或器官中的浓度高 10-10 倍,表明 PTX 在肿瘤组织中极度积累。植入载药膜后的最初 10 天内肿瘤体积保持不变,然后略有增加,这意味着肿瘤生长受到明显抑制。此外,结果表明,通过在载药层中添加 PEG 可以有效调节药物释放,可以通过添加背衬层来实现单向释放,并且药物膜可以在 300 天的药物释放后将 PC-3 前列腺癌细胞阻滞在 G2/M 期并诱导其凋亡。由于具有延长的药物释放和长期有效性的优点,这些膜具有通过局部给药进行抗肿瘤治疗的巨大潜力。

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