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阳离子固体脂质纳米粒的设计、物理特性鉴定及其在 HCT-116 和 16-HBE 细胞中的生物相容性:初步研究。

Design, Physical Characterizations, and Biocompatibility of Cationic Solid Lipid Nanoparticles in HCT-116 and 16-HBE Cells: A Preliminary Study.

机构信息

Department of Pharmaceutics, College of Pharmacy, King Khalid University, Guraiger, Abha 62529, Saudi Arabia.

Department of Pharmacology, College of Pharmacy, King Khalid University, Guraiger, Abha 62529, Saudi Arabia.

出版信息

Molecules. 2023 Feb 10;28(4):1711. doi: 10.3390/molecules28041711.

DOI:10.3390/molecules28041711
PMID:36838699
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9968044/
Abstract

In this study, pEGFP-LUC was used as a model plasmid and three distinct cationic lipids (dioleyloxy-propyl-trimethylammonium chloride [DOTMA], dioleoyl trimethylammonium propane [DOTAP], and cetylpyridinium chloride [CPC]) were tested along with PEG 5000, as a nonionic surfactant, to prepare glyceryl monostearate (GMS)-based cationic solid lipid nanoparticles (cSLNs). Both the type and quantity of surfactant had an impact on the physicochemical characteristics of the cSLNs. Thermal analysis of the greater part of the endothermic peaks of the cSLNs revealed they were noticeably different from the individual pure compounds based on their zeta potential (ZP ranging from +17 to +56 mV) and particle size (PS ranging from 185 to 244 nm). The addition of cationic surfactants was required to produce nanoparticles (NPs) with a positive surface charge. This suggested that the surfactants and extensive entanglement of the lipid matrix GMS provided support for the behavioral diversity of the cSLNs and their capacity to interface with the plasmid DNA. Additionally, hemolytic assays were used to show that the cSLNs were biocompatible with the human colon cancer HCT-116 and human bronchial epithelial 16-HBE cell lines. The DOTMA 6-based cSLN was selected as the lead cSLN for further ex vivo and in vivo investigations. Taken together, these new findings might provide some guidance in selecting surfactants to prepare extremely efficient and non-toxic cSLN-based therapeutic delivery systems (e.g., gene therapy).

摘要

在这项研究中,pEGFP-LUC 被用作模型质粒,测试了三种不同的阳离子脂质(二油酰氧基丙基三甲基氯化铵 [DOTMA]、二油酰基三甲基丙胺 [DOTAP] 和氯化十六烷基吡啶 [CPC])以及聚乙二醇 5000(一种非离子表面活性剂),以制备基于甘油单硬脂酸酯 (GMS) 的阳离子固体脂质纳米粒 (cSLN)。表面活性剂的类型和用量都会影响 cSLN 的理化特性。cSLN 的大部分吸热峰的热分析表明,它们与各自的纯化合物在 ζ 电位 (ZP 范围从 +17 到 +56 mV) 和粒径 (PS 范围从 185nm 到 244nm) 方面存在显著差异。需要添加阳离子表面活性剂才能产生带正电荷的纳米颗粒 (NPs)。这表明表面活性剂和脂质基质 GMS 的广泛缠结为 cSLN 的行为多样性及其与质粒 DNA 相互作用的能力提供了支持。此外,溶血试验用于证明 cSLN 与人类结肠癌细胞 HCT-116 和人支气管上皮细胞 16-HBE 细胞系具有生物相容性。选择 DOTMA 6 为基础的 cSLN 作为进一步的离体和体内研究的先导 cSLN。总之,这些新发现可能为选择表面活性剂制备高效、无毒的 cSLN 基治疗传递系统(如基因治疗)提供一些指导。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/713d/9968044/b7cfc45b2a4e/molecules-28-01711-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/713d/9968044/9acfd10760f2/molecules-28-01711-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/713d/9968044/70069e8d794a/molecules-28-01711-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/713d/9968044/504e6ef0fae4/molecules-28-01711-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/713d/9968044/a17dd850c658/molecules-28-01711-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/713d/9968044/1f75a3b72762/molecules-28-01711-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/713d/9968044/b7cfc45b2a4e/molecules-28-01711-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/713d/9968044/9acfd10760f2/molecules-28-01711-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/713d/9968044/70069e8d794a/molecules-28-01711-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/713d/9968044/504e6ef0fae4/molecules-28-01711-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/713d/9968044/a17dd850c658/molecules-28-01711-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/713d/9968044/1f75a3b72762/molecules-28-01711-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/713d/9968044/b7cfc45b2a4e/molecules-28-01711-g006.jpg

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