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含紫杉醇脂质体的热敏水凝胶系统用于肿瘤原位治疗的局部给药系统:更好的抗肿瘤疗效和更低的毒性

Thermosensitive Hydrogel System With Paclitaxel Liposomes Used in Localized Drug Delivery System for In Situ Treatment of Tumor: Better Antitumor Efficacy and Lower Toxicity.

作者信息

Mao Yuling, Li Xue, Chen Ge, Wang Shujun

出版信息

J Pharm Sci. 2016 Jan;105(1):194-204. doi: 10.1002/jps.24693. Epub 2016 Jan 13.

DOI:10.1002/jps.24693
PMID:26580704
Abstract

Intratumoral delivery of chemotherapeutic agents may provide drug localization within the tumor and divert the drug from nontarget organs to improve toxicity and increase efficacy. Thermosensitive injectable hydrogel system may be suitable for the treatment of pancreatic cancer. A study was carried out to examine the efficacy and toxicity of paclitaxel (PTX) liposome gel as a local chemotherapy system against pancreatic cancer in tumor-bearing mice model. The thermosensitive hydrogel we prepared had an appropriate sol-to-gel transition temperature and particle size and morphology study showed this new dosage form possessed physical stability of drug without precipitation and particle size growth of liposome. PTX-lip-gel release in vitro showed a much more slowly release than PTX-lip. The PTX-lip-gel system was proven to have a good retention inside of tumor tissue by intratumoral retention experiments. The in vivo trials showed a better balance between antitumor efficacy and systemic safety in PTX-lip-gel group than in other groups at the equal drug dose. In conclusion, the PTX-lip-gel we prepared in this study provided a high local PTX concentration, sustained and stable drug release, extend drug retention inside of tumor, and low toxicity to normal tissues.

摘要

化疗药物的瘤内递送可使药物定位于肿瘤内部,并使药物从非靶器官转移,从而改善毒性并提高疗效。热敏注射水凝胶系统可能适用于胰腺癌的治疗。开展了一项研究,以检查紫杉醇(PTX)脂质体凝胶作为局部化疗系统对荷瘤小鼠模型中胰腺癌的疗效和毒性。我们制备的热敏水凝胶具有合适的溶胶-凝胶转变温度,粒度和形态学研究表明这种新剂型具有药物的物理稳定性,无沉淀且脂质体粒径无增长。PTX-脂质体凝胶的体外释放显示比PTX-脂质体释放慢得多。通过瘤内滞留实验证明PTX-脂质体凝胶系统在肿瘤组织内具有良好的滞留性。体内试验表明,在同等药物剂量下,PTX-脂质体凝胶组在抗肿瘤疗效和全身安全性之间的平衡比其他组更好。总之,我们在本研究中制备的PTX-脂质体凝胶提供了高局部PTX浓度、持续稳定的药物释放、延长药物在肿瘤内的滞留时间以及对正常组织的低毒性。

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