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新型 PTX-HS15/T80 混合胶束:细胞毒性、药代动力学和组织分布。

New PTX-HS15/T80 Mixed Micelles: Cytotoxicity, Pharmacokinetics and Tissue Distribution.

机构信息

College of Pharmaceutical Sciences, Southwest University, Chongqing, China.

Qingdao Eye Hospital of Shandong First Medical University, Qingdao, Shandong, China.

出版信息

AAPS PharmSciTech. 2021 Jan 24;22(2):56. doi: 10.1208/s12249-021-01929-8.

DOI:10.1208/s12249-021-01929-8
PMID:33486601
Abstract

Compared with single micelle, the new PTX-HS15/T80 mixed micelle system (PTX-HS15/T80 MMs) had achieved better results in solubilization, stability, and sensitization before. Therefore, we intend to further verify the potential advantages of the mixed micelle delivery system through in vitro cytotoxicity test and animal test to understand the anticancer effect and in vivo pharmaceutical behavior of the system. In vitro cytotoxicity test showed that the new PTX-HS15/T80 MMs had a stronger ability to inhibit the proliferation of cancer cells. The results of in vivo pharmacokinetics showed that the micelle had shorter half-life, higher clearance rate, and lower blood concentration and had good blood clearance characteristics. The results of in vivo tissue distribution showed that, compared with the single micelle Taxol, the new PTX-HS15/T80 MMs had good distribution characteristics in the lung (AUC increased about 26%) and low concentration in the heart (AUC decreased about 10%). Paclitaxel was mainly metabolized through the liver and kidney. The above results suggested that the new PTX-HS15/T80 MMs may have a certain therapeutic potential against lung cancer and reduce the toxic and side effects. In general, the mixed micelle delivery system was not only simple and cheap to prepare but also had certain advantages in vitro and in vivo, indicating that the combination of surfactants provides a good choice for solving the problem of insoluble drug delivery.

摘要

与单胶束相比,新型 PTX-HS15/T80 混合胶束系统(PTX-HS15/T80 MMs)在增溶、稳定性和敏化方面已经取得了更好的效果。因此,我们打算通过体外细胞毒性试验和动物试验进一步验证混合胶束给药系统的潜在优势,以了解该系统的抗癌作用和体内药物行为。体外细胞毒性试验表明,新型 PTX-HS15/T80 MMs 具有更强的抑制癌细胞增殖能力。体内药代动力学结果表明,胶束具有更短的半衰期、更高的清除率、更低的血药浓度和良好的血液清除特性。体内组织分布结果表明,与单胶束 Taxol 相比,新型 PTX-HS15/T80 MMs 在肺部(AUC 增加约 26%)具有良好的分布特性,而在心脏中的浓度较低(AUC 降低约 10%)。紫杉醇主要通过肝脏和肾脏代谢。上述结果表明,新型 PTX-HS15/T80 MMs 可能对肺癌具有一定的治疗潜力,并降低毒性和副作用。总的来说,混合胶束给药系统不仅制备简单、廉价,而且具有一定的体外和体内优势,表明表面活性剂的组合为解决难溶性药物传递问题提供了良好的选择。

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