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载布洛芬和/或十八胺修饰的 PLGA 纳米粒的癌症治疗新方法通过评估其对细胞凋亡的影响。

Novel approaches to cancer therapy with ibuprofen-loaded and/or octadecylamine-modified PLGA nanoparticles by assessment of their effects on apoptosis.

机构信息

Department of Pharmaceutical Technology, Faculty of Pharmacy, Anadolu University, Eskişehir, Turkey.

bMedicinal Plant, Drug and Scientific Research Application and Research Center, Anadolu University (AUBİBAM), Eskişehir, Turkey.

出版信息

Drug Dev Ind Pharm. 2020 Jul;46(7):1133-1149. doi: 10.1080/03639045.2020.1776319. Epub 2020 Jun 17.

Abstract

The purpose of this study was the design ibuprofen (IBU)-loaded unique Eudragit RS 100 (ERS) and/or octadecylamine modified PLGA nanoparticles (NPs) for cancer treatment. The rational for this approach is to bring a new approach to cancer treatment with modification of IBU-loaded PLGA NPs with ERS and/or octadecylamine by means of smaller particle size (PS), cationic surface, biocompatible nature, and investigating their selective efficacy on lung cell lines (A549 lung cancer cell and CCD-19Lu normal cell line). IBU encapsulated PLGA-based NPs were prepared and characterized for physical and solid-state analyses. release, MTT, and determination of apoptotic pathways were performed. Considering characterizations, B, C, E, F, H, and K formulations with higher EE%, smaller PS and encouraging higher zeta potential were chosen for further experiments were intended to enhance anticancer action and apoptotic behavior. Formulations were showed biphasic release profile with extended release manner (Korsmeyer-Peppas model with a diffusion-controlled mechanism). The NPs effect on lung cancer cells with high specificity and affinity was demonstrated by MTT study. It was found that the effect of IBU was increased 4-28 times over the pure form. Annexin V-FITC/PI staining method, FITC Active Caspase-3 staining method, and mitochondrial membrane potential detection analyses was performed to determine the apoptotic pathways by flow cytometry. E coded NP is selected as a promising candidate with its highly specific affinity for human lung adenocarcinoma cells and could induce cell death effectively and be a potent system to treat lung cancer.

摘要

本研究旨在设计布洛芬(IBU)负载独特的 Eudragit RS 100(ERS)和/或十八烷基胺改性 PLGA 纳米粒(NPs)用于癌症治疗。这样做的理由是通过用 ERS 和/或十八烷基胺对 IBU 负载的 PLGA NPs 进行改性,带来一种新的癌症治疗方法,其特点是粒径(PS)更小、表面带正电荷、具有生物相容性,并研究其对肺细胞系(A549 肺癌细胞和 CCD-19Lu 正常细胞系)的选择性疗效。制备并对 IBU 包封的基于 PLGA 的 NPs 进行了物理和固态分析。进行了 释放、MTT 和凋亡途径的测定。考虑到特性,选择 B、C、E、F、H 和 K 制剂具有更高的 EE%、更小的 PS 和令人鼓舞的更高的 ζ 电位,用于进一步实验旨在增强抗癌作用和凋亡行为。制剂表现出双相释放曲线,具有延长释放方式(Korsmeyer-Peppas 模型,扩散控制机制)。MTT 研究表明,NPs 对肺癌细胞具有高特异性和亲和力的作用。发现 IBU 的作用比纯形式增加了 4-28 倍。通过流式细胞术,用 Annexin V-FITC/PI 染色法、FITC 活性 Caspase-3 染色法和线粒体膜电位检测分析来确定凋亡途径。E 编码 NP 被选为一种很有前途的候选物,因为它对人肺腺癌细胞具有高度特异性亲和力,能够有效诱导细胞死亡,并成为治疗肺癌的有效系统。

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