Combination of DMDD with Nanoparticles Effective Against Diabetic Kidney Disease in vitro.

IF 6.6 2区医学 Q1 NANOSCIENCE & NANOTECHNOLOGY

International Journal of Nanomedicine Pub Date : 2024-11-23 eCollection Date: 2024-01-01 DOI:10.2147/IJN.S475840

Xiao-Man Huang, Yan-Xiang Guo, Qiu-Ling Pang, Xiao-Yi Yan, Hui Yan, Jing-Yi Li, Gan-Ling Tang, Hui-Xian Jiang, Hong-Liang Zhang

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引用次数: 0

Abstract

Purpose: 2-Dodecyl-6-methoxy-2,5-diene-1,4-cyclohexanedione (DMDD), isolated from Averrhoa carambola L. root, has demonstrated the potential to reduce blood sugar levels. However, DMDD has poor solubility and bioavailability. This study aimed to formulate DMDD-loaded nanoparticles (DMDD-NPs) using chitosan crosslinked with sodium tripolyphosphate through the ionic crosslinking method and to investigate their effect on diabetic kidney disease (DKD) treatment by inhibiting the development of the epithelial-mesenchymal transition (EMT).

Methods: DMDD-NPs were prepared by ionic crosslinking with sodium tripolyphosphate, optimizing six factors that affect nanoparticle characteristics, including particle size and zeta potential. Encapsulation efficiency (EE) and drug loading rate (DL) were optimized using a Box-Behnken design. The structure and characteristics of DMDD-NPs, including size, EE, DL, and release rates, were analyzed. Cytotoxicity was assessed using the Cell Counting Kit-8 (CCK-8) assay, while the migration capacity of HK-2 cells was evaluated through scratch-wound assays. The expression of EMT-related markers (E-cadherin, Vimentin, and TGF-β1) was assessed by qRT-PCR.

Results: The optimized formulation for DMDD-NPs was CS:TPP:DMDD = 10:3:3 (w), at pH 3.5, with 1.0 mg/mL of CS and stirring at 500 rpm for 30 min. In these conditions, the nanoparticles had a particle size of 320.37 ± 2.93 nm, an EE of 85.09 ± 1.43%, and a DL of 15.88 ± 0.51%. The DMDD-NPs exhibited a spherical shape, no leakage and minimal adhesion. The optimal freeze-drying protectant was a combination of 0.025% mannitol and 0.025% lactose. The drug release followed the Higuchi model. DMDD-NPs improved HK-2 cell proliferation at lower concentrations (<24 μg/mL) and showed greater cell migration inhibition than DMDD. DMDD-NPs promoted E-cadherin expression and inhibited vimentin and TGF-β1 expression, suggesting their potential role in preventing EMT for DKD treatment.

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DMDD与纳米颗粒联合抗糖尿病肾病的体外实验研究

目的：从杨桃根中分离得到的2-十二烷基-6-甲氧基-2,5-二烯-1,4-环己二酮（DMDD）具有降血糖的作用。然而，DMDD具有较差的溶解度和生物利用度。本研究旨在通过离子交联法将壳聚糖与三聚磷酸钠交联制备负载dmdd的纳米颗粒（DMDD-NPs），并通过抑制上皮-间质转化（EMT）的发展来研究其对糖尿病肾病（DKD）的治疗作用。方法：采用三聚磷酸钠离子交联法制备DMDD-NPs，优化粒径、zeta电位等6个影响纳米颗粒特性的因素。采用Box-Behnken设计优化包封效率（EE）和载药率（DL）。分析了DMDD-NPs的结构和特征，包括大小、EE、DL和释放率。采用细胞计数试剂盒-8 （CCK-8）法评估细胞毒性，通过划痕法评估HK-2细胞的迁移能力。qRT-PCR检测emt相关标志物E-cadherin、Vimentin、TGF-β1的表达。结果：DMDD - nps的最佳配方为：CS:TPP:DMDD = 10:3:3 (w)， pH为3.5，CS浓度为1.0 mg/mL， 500 rpm搅拌30 min。在此条件下，纳米颗粒粒径为320.37±2.93 nm， EE为85.09±1.43%，DL为15.88±0.51%。DMDD-NPs呈球形，无渗漏，粘附最小。最佳冻干保护剂为0.025%甘露醇和0.025%乳糖的组合。药物释放遵循Higuchi模型。低浓度的DMDD-NPs促进HK-2细胞增殖(

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来源期刊

International Journal of Nanomedicine NANOSCIENCE & NANOTECHNOLOGY-PHARMACOLOGY & PHARMACY

CiteScore

14.40

自引率

3.80%

发文量

511

审稿时长

1.4 months

期刊介绍： The International Journal of Nanomedicine is a globally recognized journal that focuses on the applications of nanotechnology in the biomedical field. It is a peer-reviewed and open-access publication that covers diverse aspects of this rapidly evolving research area. With its strong emphasis on the clinical potential of nanoparticles in disease diagnostics, prevention, and treatment, the journal aims to showcase cutting-edge research and development in the field. Starting from now, the International Journal of Nanomedicine will not accept meta-analyses for publication.