{"title":"Combination of DMDD with Nanoparticles Effective Against Diabetic Kidney Disease in vitro.","authors":"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","doi":"10.2147/IJN.S475840","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>2-Dodecyl-6-methoxy-2,5-diene-1,4-cyclohexanedione (DMDD), isolated from <i>Averrhoa carambola L</i>. 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).</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"19 ","pages":"12439-12460"},"PeriodicalIF":6.6000,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11602433/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Journal of Nanomedicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2147/IJN.S475840","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"NANOSCIENCE & NANOTECHNOLOGY","Score":null,"Total":0}
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.
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.
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