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用于癌症治疗且副作用降低的载卡巴他赛纳米载体

Cabazitaxel-Loaded Nanocarriers for Cancer Therapy with Reduced Side Effects.

作者信息

Kommineni Nagavendra, Mahira Shaheen, Domb Abraham J, Khan Wahid

机构信息

Department of Pharmaceutics, National Institute of Pharmaceutical Education & Research (NIPER), Hyderabad 500037, India.

School of Pharmacy-Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 91120, Israel.

出版信息

Pharmaceutics. 2019 Mar 25;11(3):141. doi: 10.3390/pharmaceutics11030141.

Abstract

Jevtana is a micellar cabazitaxel (CBZ) solution that was approved for prostate cancer in 2010, and recently, this drug has been reported for breast cancer. The purpose of this study is to evaluate the mediated delivery of CBZ via liposomes and nanoparticles (NPs) for the treatment of breast cancer and compare these with a micellar formulation that is currently in clinical use. CBZ-loaded nanocarriers were prepared with particle sizes between 70⁻110 nm, and with the sustained in vitro release of CBZ for more than 28 days. Cytotoxicity studies on MCF-7 and MDA-MB-231 cells demonstrated the toxic potential of these nanocarriers. Cellular internalization revealed that NPs and liposomes have better permeability than micelles. Cell cycle analysis and apoptosis studies on MCF-7 and MDA-MB-231 cells confirmed G2/M phase arrest as well as cell death due to apoptosis and necrosis, where formulations were found to be effective compared to a micellar CBZ solution. Results from pharmacokinetic studies revealed that there is an increased circulation half-life and mean residence time for CBZ liposomes and NPs in comparison with a micellar CBZ solution. CBZ liposomes and NPs showed a reduction in hemolysis and neutropenia in comparison with a micellar CBZ solution in rats.

摘要

捷维坦纳是一种胶束型卡巴他赛(CBZ)溶液,于2010年被批准用于治疗前列腺癌,最近,该药物也被报道可用于治疗乳腺癌。本研究的目的是评估通过脂质体和纳米颗粒(NPs)介导递送CBZ用于治疗乳腺癌的效果,并将其与目前临床使用的胶束制剂进行比较。制备了粒径在70-110nm之间的负载CBZ的纳米载体,其CBZ在体外可持续释放超过28天。对MCF-7和MDA-MB-231细胞的细胞毒性研究证明了这些纳米载体的毒性潜力。细胞内化显示,NPs和脂质体比胶束具有更好的渗透性。对MCF-7 and MDA-MB-231细胞的细胞周期分析和凋亡研究证实了G2/M期阻滞以及由于凋亡和坏死导致的细胞死亡,发现与胶束型CBZ溶液相比,这些制剂是有效的。药代动力学研究结果显示,与胶束型CBZ溶液相比,CBZ脂质体和NPs的循环半衰期和平均驻留时间有所增加。与胶束型CBZ溶液相比,CBZ脂质体和NPs在大鼠中显示出溶血和中性粒细胞减少的情况有所减轻。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d677/6470818/b6c5b22cda89/pharmaceutics-11-00141-g001.jpg

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