Limited cellular uptake of liposomes: Might thiolated phospholipids hold the key?

IF 5.3 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics Pub Date : 2024-10-16 DOI:10.1016/j.ijpharm.2024.124812

Daniel Stengel, Zeliha Duygu Özdal, Martyna Truszkowska, Ahmad Saleh, Anna Seybold, Andreas Bernkop-Schnürch

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引用次数: 0

Abstract

Aim: It was the aim of this study to evaluate the impact of surface thiolation on cellular uptake of liposomes.

Methods: Liposomes were prepared via the thin lipid film method, incorporating cholesterol, dipalmitoylphosphatidylcholin (DPPC) and 1,2-dipalmitoyl-sn-glycero-3-phosphothioethanol). The characterization of liposomes included size, polydispersity index, surface morphology, zeta potential and stability in simulated gastric and intestinal fluid. Hemocompatibility and cytotoxicity of liposomes were investigated. Cellular uptake studies were performed on Caco-2, HeLa, HEK and SW620 cells, involving both quantitative analysis through flow cytometry and qualitative evaluation via confocal microscopy. Additionally, we investigated the impact of an oxidizing agent on thiol-dependent uptake.

Results: Non-thiolated and thiolated liposomes exhibited a size of 149 nm to 274 nm and a PDI between 0.3 and 0.45. Liposomes were stable in simulated intestinal and gastric fluid. Hemocompatibility studies and cytocompatibility studies of liposomes showed negligible toxic effects of liposomes. Cellular uptake of thiolated liposomes was 1.8-, 2.1-, 5.4- and 1.4-fold enhanced in comparison to non-thiolated liposomes on Caco-2, HEK, HELA and SW620 cells, respectively. The results were qualitatively verified by confocal microscopy. Thiol dependent uptake was influenced by oxidizing agents on HeLa cells.

Conclusion: Surface thiolation represents a promising approach to enhance cellular uptake of liposomes.

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细胞对脂质体的吸收有限：硫醇化磷脂可能是关键所在？

目的：本研究旨在评估脂质体表面硫醇化对细胞吸收的影响：脂质体的制备采用薄膜脂质法，其中包含胆固醇、二棕榈酰磷脂酰胆碱（DPPC）和 1,2-二棕榈酰-sn-甘油-3-磷硫乙醇。）脂质体的表征包括尺寸、多分散指数、表面形态、ZETA电位以及在模拟胃液和肠液中的稳定性。还研究了脂质体的血液相容性和细胞毒性。对 Caco-2、HeLa、HEK 和 SW620 细胞进行了细胞吸收研究，包括通过流式细胞仪进行定量分析和通过共聚焦显微镜进行定性评估。此外，我们还研究了氧化剂对硫醇依赖性摄取的影响：结果：非硫醇化和硫醇化脂质体的大小在 149 纳米到 274 纳米之间，PDI 在 0.3 到 0.45 之间。脂质体在模拟肠液和胃液中稳定。脂质体的血液相容性研究和细胞相容性研究表明，脂质体的毒性作用可以忽略不计。在 Caco-2、HEK、HELA 和 SW620 细胞上，硫醇脂质体的细胞摄取量分别是非硫醇脂质体的 1.8 倍、2.1 倍、5.4 倍和 1.4 倍。共聚焦显微镜对结果进行了定性验证。在 HeLa 细胞上，硫醇依赖性吸收受到氧化剂的影响：结论：表面硫醇化是提高脂质体细胞摄取率的一种可行方法。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

International Journal of Pharmaceutics 医学-药学

CiteScore

10.70

自引率

8.60%

发文量

951

审稿时长

72 days

期刊介绍： The International Journal of Pharmaceutics is the third most cited journal in the "Pharmacy & Pharmacology" category out of 366 journals, being the true home for pharmaceutical scientists concerned with the physical, chemical and biological properties of devices and delivery systems for drugs, vaccines and biologicals, including their design, manufacture and evaluation. This includes evaluation of the properties of drugs, excipients such as surfactants and polymers and novel materials. The journal has special sections on pharmaceutical nanotechnology and personalized medicines, and publishes research papers, reviews, commentaries and letters to the editor as well as special issues.