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用于前列腺癌的载有吡罗昔康的核壳型混合纳米载体的Box-Behnken设计优化及基于体外细胞的评价

Box-Behnken design optimization and in vitro cell based evaluation of piroxicam loaded core-shell type hybrid nanocarriers for prostate cancer.

作者信息

Sengel-Turk Ceyda Tuba, Ozkan Erva, Bakar-Ates Filiz

机构信息

Ankara University, Faculty of Pharmacy, Department of Pharmaceutical Technology, 06100, Anadolu, Ankara, Turkey.

Ankara University, Faculty of Pharmacy, Department of Biochemistry, 06100, Anadolu, Ankara, Turkey.

出版信息

J Pharm Biomed Anal. 2022 Jul 15;216:114799. doi: 10.1016/j.jpba.2022.114799. Epub 2022 Apr 25.

Abstract

In the present research, piroxicam entrapped core-shell lipid-polymer hybrid nanocarriers were developed and also evaluated in terms of nanoparticle features and cell-based in vitro efficacy on prostate cancer cells. Box-Behnken optimization approach was implemented to evaluate the impact of the input variables, namely phospholipid/PLGA ratio, total lipids/lecithin molar ratio, and piroxicam concentration, on two output variables: particle size and entrapment efficiency. Surface charge, size distribution, morphological structure of particles, drug release profiles, presence of outer lipid shell, thermal profile and possible interactions and storage stability of core-shell nanocarriers of piroxicam were studied as particle features. Cell viability, apoptosis and cell cycle arrest studies were utilized for in vitro cell-based evaluation of the core-shell nanosystems. The hybrid nanocarrier formulation with a particle size of 119.2 nm and an entrapment efficiency of 91.7% at the center point of the design was selected as the optimized formulation according to the desired function (d) method applied within the scope of the Box-Behnken design approach and RSM strategy. The cell viability and apoptosis experiments were performed on the optimized nanocarrier. In conclusion, this study demonstrates that the optimized core-shell nanoformulation of piroxicam is a more promising strategy in the treatment of prostate cancer compared to the pure molecule.

摘要

在本研究中,开发了包载吡罗昔康的核壳脂质-聚合物杂化纳米载体,并从纳米颗粒特性以及对前列腺癌细胞的体外细胞疗效方面进行了评估。采用Box-Behnken优化方法来评估输入变量,即磷脂/聚乳酸-羟基乙酸共聚物(PLGA)比例、总脂质/卵磷脂摩尔比和吡罗昔康浓度,对两个输出变量:粒径和包封率的影响。研究了吡罗昔康核壳纳米载体的表面电荷、粒径分布、颗粒形态结构、药物释放曲线、外层脂质壳的存在情况、热特性以及可能的相互作用和储存稳定性等颗粒特性。利用细胞活力、凋亡和细胞周期阻滞研究对核壳纳米系统进行体外细胞评估。根据Box-Behnken设计方法和响应面法(RSM)策略范围内应用的期望函数(d)方法,选择设计中心点处粒径为119.2 nm且包封率为91.7%的杂化纳米载体制剂作为优化制剂。对优化后的纳米载体进行了细胞活力和凋亡实验。总之,本研究表明,与纯分子相比,优化后的吡罗昔康核壳纳米制剂在前列腺癌治疗中是一种更有前景的策略。

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