基于 mcl-Polyhydroxyalkanoate 和阳离子脂质体的稳定聚合物-脂质混合纳米颗粒用于 mRNA 输送。

IF 4.9 3区 医学 Q1 PHARMACOLOGY & PHARMACY Pharmaceutics Pub Date : 2024-10-07 DOI:10.3390/pharmaceutics16101305
Sergey M Shishlyannikov, Ilya N Zubkov, Vera V Vysochinskaya, Nina V Gavrilova, Olga A Dobrovolskaya, Ekaterina A Elpaeva, Mikhail A Maslov, Andrey Vasin
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引用次数: 0

摘要

背景/目标:开发聚合物-脂质杂化纳米颗粒(PLNs)是一个前景广阔的研究领域,因为它有助于提高阳离子脂质载体的稳定性。混合型 PLNs 是一种核壳纳米粒子结构,它结合了聚合物纳米粒子和脂质体的优点,尤其是在物理稳定性和生物相容性方面。聚羟基烷酸酯(PHA)等天然聚合物可用作制备 PLNs 的基质。制备方法在这项研究中,我们首先利用阳离子脂质体(CL)制备了稳定的阳离子杂化聚合氯化萘(PLNs),该脂质体由多阳离子脂质 2X3 (1,26-双(胆甾-5-烯-3β-基氧羰基氨基)-7,11,16、20-tetraazahexacosane tetrahydrochloride)、辅助脂质 DOPE(1,2-dioleoyl-sn-glycero-3-phosphoethanolamine)和疏水性聚合物 mcl-PHA,后者由土壤中的 helmantisensis P1 假单胞菌产生。研究结果新的聚合物脂质载体有效地将模型 mRNA-eGFP(增强型绿色荧光蛋白 mRNA)包裹并输送到 BHK-21 细胞中。然后,我们利用动态光散射数据、电泳迁移率和透射电子显微镜技术评估了 mcl-PHA 在提高阳离子 PLN 在离子溶液中的稳定性方面的作用。得出结论:结果表明,增加 PBS(磷酸盐缓冲盐水)的浓度会导致 CLs 的稳定性降低。在高浓度的磷酸盐缓冲盐溶液中,CLs 会聚集。与此相反,等渗 PBS 的存在不会导致 PLNs 的聚集,在 +4 °C 下储存 120 小时后,颗粒仍然保持稳定。这些结果表明,PLNs 有望用于进一步的体内核酸递送研究。
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Stable Polymer-Lipid Hybrid Nanoparticles Based on mcl-Polyhydroxyalkanoate and Cationic Liposomes for mRNA Delivery.

Background/Objectives: The development of polymer-lipid hybrid nanoparticles (PLNs) is a promising area of research, as it can help increase the stability of cationic lipid carriers. Hybrid PLNs are core-shell nanoparticle structures that combine the advantages of both polymer nanoparticles and liposomes, especially in terms of their physical stability and biocompatibility. Natural polymers such as polyhydroxyalkanoate (PHA) can be used as a matrix for the PLNs' preparation. Methods: In this study, we first obtained stable cationic hybrid PLNs using a cationic liposome (CL) composed of a polycationic lipid 2X3 (1,26-bis(cholest-5-en-3β-yloxycarbonylamino)-7,11,16,20-tetraazahexacosane tetrahydrochloride), helper lipid DOPE (1,2-dioleoyl-sn-glycero-3-phosphoethanolamine), and the hydrophobic polymer mcl-PHA, which was produced by the soil bacterium Pseudomonas helmantisensis P1. Results: The new polymer-lipid carriers effectively encapsulated and delivered model mRNA-eGFP (enhanced green fluorescent protein mRNA) to BHK-21 cells. We then evaluated the role of mcl-PHA in increasing the stability of cationic PLNs in ionic solutions using dynamic light scattering data, electrophoretic mobility, and transmission electron microscopy techniques. Conclusions: The results showed that increasing the concentration of PBS (phosphate buffered saline) led to a decrease in the stability of the CLs. At high concentrations of PBS, the CLs aggregate. In contrast, the presence of isotonic PBS did not result in the aggregation of PLNs, and the particles remained stable for 120 h when stored at +4 °C. The obtained results show that PLNs hold promise for further in vivo studies on nucleic acid delivery.

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来源期刊
Pharmaceutics
Pharmaceutics Pharmacology, Toxicology and Pharmaceutics-Pharmaceutical Science
CiteScore
7.90
自引率
11.10%
发文量
2379
审稿时长
16.41 days
期刊介绍: Pharmaceutics (ISSN 1999-4923) is an open access journal which provides an advanced forum for the science and technology of pharmaceutics and biopharmaceutics. It publishes reviews, regular research papers, communications,  and short notes. Covered topics include pharmacokinetics, toxicokinetics, pharmacodynamics, pharmacogenetics and pharmacogenomics, and pharmaceutical formulation. Our aim is to encourage scientists to publish their experimental and theoretical details in as much detail as possible. There is no restriction on the length of the papers. The full experimental details must be provided so that the results can be reproduced.
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