Non-lamellar lyotropic liquid crystalline nanoparticles as nanocarriers for enhanced drug encapsulation of atorvastatin calcium and proanthocyanidins

IF 3.4 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Chemistry and Physics of Lipids Pub Date : 2024-02-05 DOI:10.1016/j.chemphyslip.2024.105377

Mardhiah Maslizan , Muhammad Salahuddin Haris , Mokrish Ajat , Siti Nurul Ain Md Jamil , Shah Christirani Azhar , N. Idayu Zahid , Intan Diana Mat Azmi

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Abstract

Atorvastatin calcium (ATV) and proanthocyanidins (PAC) have a strong antioxidant activity, that can benefit to reduce the atherosclerotic plaque progression. Unfortunately, the bioavailability of ATV is greatly reduced due to its limited drug solubility while the PAC drug is unstable upon exposure to the atmospheric oxygen. Herein, the lyotropic liquid crystalline nanoparticles (LLCNPs) constructed by a binary mixture of soy phosphatidylcholine (SPC) and citric acid ester of monoglyceride (citrem) at different weight ratios were used to encapsulate the hydrophobic ATV and hydrophilic PAC. The LLCNPs were further characterized by small-angle X-ray scattering and dynamic light scattering. Depending on the lipid composition, the systems have a size range of 140–190 nm and were able to encapsulate both drugs in the range of 90–100%. Upon increasing the citrem content of drug-loaded LLCNPs, the hexosomes (H₂) was completely transformed to an emulsified inverse micellar (L₂). The optimum encapsulation efficiency (EE) of ATV and PAC were obtained in citrem/SPC weight ratio 4:1 (L₂) and 1:1 (H₂), respectively. There was a substantial change in the mean size and PDI of the nanoparticles upon 30 days of storage with the ATV-loaded LLCNPs exhibiting greater colloidal instability than PAC-loaded LLCNPs. The biphasic released pattern (burst released at the initial stage followed by the sustained released at the later stage) was perceived in ATV formulation, while the burst drug released pattern was observed in PAC formulations that could be attributed by its internal H₂ structure. Interestingly, the cytokine studies showed that the PAC-LLCNPs promisingly up regulate the expressions of tumor necrosis factor-alpha (TNF-α) better than the drug-free and ATV-loaded LLCNPs samples. The structural tunability of citrem/SPC nanoparticles and their effect on physicochemical characteristic, biological activities and potential as an alternative drug delivery platform in the treatment of atherosclerosis are discussed.

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作为纳米载体增强阿托伐他汀钙和原花青素的药物包封的非喇嘛溶液结晶纳米颗粒

阿托伐他汀钙片（ATV）和原花青素（PAC）具有很强的抗氧化活性，能有效减少动脉粥样硬化斑块的形成。遗憾的是，由于药物溶解度有限，ATV 的生物利用度大大降低，而 PAC 药物在暴露于大气中的氧气时不稳定。本文采用大豆磷脂酰胆碱（SPC）和柠檬酸单甘酯（citrem）的二元混合物以不同重量比构建的溶胀性液晶纳米颗粒（LLCNPs）来封装疏水性的亚视和亲水性的PAC。通过小角 X 射线散射和动态光散射对 LLCNPs 进行了进一步表征。根据脂质成分的不同，该系统的尺寸范围为 140-190 nm，对两种药物的包裹率在 90-100% 之间。随着载药LLCNPs中柠檬烷含量的增加，六聚体（H2）完全转变为乳化反胶束（L2）。柠檬醛/SPC重量比分别为4:1（L2）和1:1（H2）时，ATV和PAC获得了最佳包封效率（EE）。储存 30 天后，纳米颗粒的平均尺寸和 PDI 发生了很大变化，ATV 负载的 LLCNPs 比 PAC 负载的 LLCNPs 表现出更大的胶体不稳定性。ATV 制剂出现了双相释放模式（初期猝灭释放，后期持续释放），而 PAC 制剂则出现了猝灭药物释放模式，这可能与其内部 H2 结构有关。有趣的是，细胞因子研究表明，PAC-LLCNPs 对肿瘤坏死因子-α（TNF-α）表达的调节作用优于无药和含有 ATV 的 LLCNPs 样品。本文讨论了柠檬醛/SPC 纳米粒子的结构可调性及其对理化特性、生物活性的影响，以及作为治疗动脉粥样硬化的替代给药平台的潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Chemistry and Physics of Lipids 生物-生化与分子生物学

CiteScore

7.60

自引率

2.90%

发文量

审稿时长

40 days

期刊介绍： Chemistry and Physics of Lipids publishes research papers and review articles on chemical and physical aspects of lipids with primary emphasis on the relationship of these properties to biological functions and to biomedical applications. Accordingly, the journal covers: advances in synthetic and analytical lipid methodology; mass-spectrometry of lipids; chemical and physical characterisation of isolated structures; thermodynamics, phase behaviour, topology and dynamics of lipid assemblies; physicochemical studies into lipid-lipid and lipid-protein interactions in lipoproteins and in natural and model membranes; movement of lipids within, across and between membranes; intracellular lipid transfer; structure-function relationships and the nature of lipid-derived second messengers; chemical, physical and functional alterations of lipids induced by free radicals; enzymatic and non-enzymatic mechanisms of lipid peroxidation in cells, tissues, biofluids; oxidative lipidomics; and the role of lipids in the regulation of membrane-dependent biological processes.