Liver-Targeting Composite Nanocarrier Delivery System Based on Chitosan Nanoparticles and Phospholipid Complexes.

IF 1.6 4区 医学 Q4 BIOCHEMICAL RESEARCH METHODS
Fanming Kong, Jingmeng Sun, Yue Hu, Wenkai Huo, Dongdong Li, Weiyu Zhang
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引用次数: 0

Abstract

Liver fibrosis is mainly caused by excessive accumulation of extracellular matrix and structural changes in the liver, ultimately leading to cirrhosis if left untreated. Reducing hyaluronan synthesis by inhibiting hyaluronic acid deposition or regulating the expression of hyaluronic synthase can ameliorate liver fibrosis symptoms. In this study, we aimed to improve the bioavailability and liver-targeting capacity of hydroxymethyl coumarin (4-MU) using a newly developed phospholipid complex chitosan nanoparticle (4-MU PC/CNP) optimized using the Box-Behnken design. The composite nanocarrier delivery system was formulated using solvent evaporation technology, and formulation and process parameters were evaluated. Furthermore, 4-MU PC/CNPs and their pharmacokinetics were characterized. The established 4-MU PC/CNPs had an average particle size of 153.07 ± 0.29 nm, a polydispersity index value of 0.383, and a positive zeta potential of ∼35.4 mV. Compared with 4-MUs, 4-MU PC/CNPs exhibited significantly improved water solubility, faster plasma clearance and tissue distribution, and better liver targeting. Pharmacokinetic analysis showed that the oral bioavailability of 4-MU in 4-MU PC/CNPs was significantly higher than that of simple 4-MU. In conclusion, 4-MU PC improved drug lipid (oil-water distribution coefficient of 1.31 ± 0.03) and water solubilities (2.05 times the drug substance). 4-MU PC/CNPs significantly improved 4-MU oral bioavailability, representing a promising approach for enhancing drug solubility. This study demonstrates that the targeting parameters of 4-MU PC/CNPs in the liver were all greater than 1, indicating that they specifically targeted the liver, thereby potentially alleviating liver fibrosis.

基于壳聚糖纳米颗粒和磷脂复合物的肝脏靶向复合纳米载体输送系统
肝纤维化主要是由于肝脏细胞外基质过度积聚和结构变化引起的,如不及时治疗,最终会导致肝硬化。通过抑制透明质酸沉积或调节透明质酸合成酶的表达来减少透明质酸的合成,可以改善肝纤维化症状。在本研究中,我们利用新开发的磷脂复合壳聚糖纳米粒子(4-MU PC/CNP),采用盒-贝肯(Box-Behnken)设计进行优化,旨在提高羟甲基香豆素(4-MU)的生物利用度和肝脏靶向能力。利用溶剂蒸发技术配制了复合纳米载体给药系统,并对配方和工艺参数进行了评估。此外,还对 4-MU PC/CNP 及其药代动力学进行了表征。所制备的 4-MU PC/CNPs 平均粒径为 153.07 ± 0.29 nm,多分散指数值为 0.383,正 Zeta 电位为 35.4 mV。与 4-MUs 相比,4-MU PC/CNPs 的水溶性明显提高,血浆清除率和组织分布更快,肝脏靶向性更好。药代动力学分析表明,4-MU PC/CNPs 中 4-MU 的口服生物利用度明显高于单纯的 4-MU。总之,4-MU PC 提高了药物的脂溶性(油水分配系数为 1.31 ± 0.03)和水溶性(2.05 倍于药物物质)。4-MU PC/CNPs 显著提高了 4-MU 的口服生物利用度,是一种很有前景的提高药物溶解度的方法。这项研究表明,4-MU PC/CNPs 在肝脏中的靶向参数均大于 1,这表明它们能特异性地靶向肝脏,从而有可能缓解肝纤维化。
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来源期刊
Assay and drug development technologies
Assay and drug development technologies 医学-生化研究方法
CiteScore
3.60
自引率
0.00%
发文量
33
审稿时长
>12 weeks
期刊介绍: ASSAY and Drug Development Technologies provides access to novel techniques and robust tools that enable critical advances in early-stage screening. This research published in the Journal leads to important therapeutics and platforms for drug discovery and development. This reputable peer-reviewed journal features original papers application-oriented technology reviews, topical issues on novel and burgeoning areas of research, and reports in methodology and technology application. ASSAY and Drug Development Technologies coverage includes: -Assay design, target development, and high-throughput technologies- Hit to Lead optimization and medicinal chemistry through preclinical candidate selection- Lab automation, sample management, bioinformatics, data mining, virtual screening, and data analysis- Approaches to assays configured for gene families, inherited, and infectious diseases- Assays and strategies for adapting model organisms to drug discovery- The use of stem cells as models of disease- Translation of phenotypic outputs to target identification- Exploration and mechanistic studies of the technical basis for assay and screening artifacts
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