DOX-TPP/HA-ss-OA纳米颗粒的制备、体外药物释放行为研究和体外抗增殖活性评估。

IF 1.6 4区 医学 Q4 BIOCHEMICAL RESEARCH METHODS
Xuanting Fei, Qiaohong Hu
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引用次数: 0

摘要

研究目的本研究旨在利用线粒体靶向原药多柔比星-三苯基膦(DOXTPP)和还原敏感性两性聚合物透明质酸-二硫代-油酸(HAss- OA),开发 DOX-TPP/HA-ss-OA 纳米粒子并确定其特性。研究重点是评估这些纳米颗粒在不同谷胱甘肽(GSH)浓度下的药物释放行为及其体外抗肿瘤活性:方法:采用探针超声技术制备 DOX-TPP/HA-ss-OA 纳米粒子。研究考察了不同有机溶剂对药物负载能力和封装效率的影响,以确定最佳条件。采用单因素实验设计来优化制剂过程。测量了包括粒度和 zeta 电位在内的关键参数,以评估纳米粒子的稳定性和性能。采用动态透析法评估不同 GSH 浓度介质中还原敏感药物释放特性。采用 MTT 法分析纳米颗粒对人乳腺癌细胞(MCF-7)和耐药细胞(MCF-7/ADR)的生长抑制作用:DOX-TPP/HA-ss-OA纳米颗粒的优化制备工艺包括:药物剂量为2.0毫克,油水体积比为1:5,超声功率为500瓦,超声时间为15分钟。纳米颗粒的平均粒径为 203.72 ± 2.30 nm,zeta 电位为 25.82 ± 0.58 mV,显示出良好的稳定性和有效的给药特性。纳米颗粒在 pH 值为 7.4 的磷酸盐缓冲溶液(PBS)中表现出缓慢、持续的 DOX-TPP 释放,而在高浓度 GSH 溶液中则表现出加速释放,显示出还原反应性药物释放。体外研究表明,DOX-TPP/HA-ss-OA 纳米颗粒以剂量依赖的方式显著抑制了 MCF-7 和 MCF-7/ADR 细胞的增殖,与游离 DOX 和其他制剂相比,疗效更佳:结论:DOX-TPP/HA-ss-OA 纳米颗粒具有出色的还原敏感性、体外有效抑制肿瘤细胞生长以及克服耐药性的能力。包括粒度和 zeta 电位在内的测量结果表明它们适合作为药物载体,凸显了它们在癌症靶向治疗和进一步开发方面的潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Preparation of DOX-TPP/HA-ss-OA Nanoparticles, Investigation of Drug Release Behavior In Vitro, and Evaluation of Anti-proliferative Activity In Vitro.

Objective: This study aimed to develop and characterize DOX-TPP/HA-ss-OA nanoparticles, utilizing the mitochondria-targeting prodrug doxorubicin-triphenylphosphine (DOXTPP) and a reduction-sensitive amphiphilic polymer, hyaluronic acid-disulfide-oleic acid (HAss- OA). The research focused on evaluating the drug release behavior of these nanoparticles under varying glutathione (GSH) concentrations and their anti-tumor activity in vitro.

Methods: DOX-TPP/HA-ss-OA nanoparticles were prepared using probe ultrasound technology. The study examined the impact of different organic solvents on drug loading capacity and encapsulation efficiency to determine the optimal conditions. A single-factor experimental design was used to optimize the formulation process. Key parameters, including particle size and zeta potential, were measured to assess nanoparticle stability and performance. The dynamic dialysis method was employed to evaluate the reduction-sensitive drug release characteristics in media with different GSH concentrations. The MTT assay was used to analyze the growth-inhibitory effects of the nanoparticles on human breast cancer cells (MCF-7) and drug-resistant cells (MCF-7/ADR).

Results: The optimized preparation process for DOX-TPP/HA-ss-OA nanoparticles included a drug dosage of 2.0 mg, an oil-to-water volume ratio of 1:5, ultrasonic power of 500 W, and ultrasonic time of 15 minutes. The nanoparticles had an average particle size of 203.72 ± 2.30 nm and a zeta potential of 25.82 ± 0.58 mV, indicating favorable stability and effective drug delivery properties. The nanoparticles exhibited a slow, sustained release of DOX-TPP in pH 7.4 phosphate buffer solution (PBS) and accelerated release in high GSH concentrations, demonstrating reduction-responsive drug release. In vitro studies showed that DOX-TPP/HA-ss-OA nanoparticles significantly inhibited the proliferation of MCF-7 and MCF-7/ADR cells in a dosedependent manner, with enhanced efficacy compared to free DOX and other formulations.

Conclusion: DOX-TPP/HA-ss-OA nanoparticles demonstrate excellent reduction sensitivity, effective tumor cell growth inhibition in vitro, and the ability to overcome drug resistance. Including particle size and zeta potential measurements supports their suitability as drug carriers, highlighting their potential for targeted cancer therapy and further development.

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来源期刊
CiteScore
3.10
自引率
5.60%
发文量
327
审稿时长
7.5 months
期刊介绍: Combinatorial Chemistry & High Throughput Screening (CCHTS) publishes full length original research articles and reviews/mini-reviews dealing with various topics related to chemical biology (High Throughput Screening, Combinatorial Chemistry, Chemoinformatics, Laboratory Automation and Compound management) in advancing drug discovery research. Original research articles and reviews in the following areas are of special interest to the readers of this journal: Target identification and validation Assay design, development, miniaturization and comparison High throughput/high content/in silico screening and associated technologies Label-free detection technologies and applications Stem cell technologies Biomarkers ADMET/PK/PD methodologies and screening Probe discovery and development, hit to lead optimization Combinatorial chemistry (e.g. small molecules, peptide, nucleic acid or phage display libraries) Chemical library design and chemical diversity Chemo/bio-informatics, data mining Compound management Pharmacognosy Natural Products Research (Chemistry, Biology and Pharmacology of Natural Products) Natural Product Analytical Studies Bipharmaceutical studies of Natural products Drug repurposing Data management and statistical analysis Laboratory automation, robotics, microfluidics, signal detection technologies Current & Future Institutional Research Profile Technology transfer, legal and licensing issues Patents.
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