Drug-loaded composite materials based on polysaccharide carriers for alleviating myocardial cell damage

IF 2.4 3区化学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Carbohydrate Research Pub Date : 2025-06-06 DOI:10.1016/j.carres.2025.109574

Lingling Sun , Lifeng Zhu , Xiaoci Li , Weimin Jiang

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引用次数: 0

Abstract

Heart failure, a leading cause of mortality among cardiovascular disease patients, is primarily a consequence of chronic heart failure (CHF) and myocardial tissue damage associated with apoptosis. Leveraging the pharmacological success of Dapagliflozin, an SGLT-2 inhibitor known for reducing glucose reabsorption and its preventative efficacy against cardiovascular diseases, we have engineered and synthesized a novel derivative, compound 2, to enhance therapeutic outcomes. Furthermore, we utilized chitosan (CS) as a carrier matrix and integrated a bioactive compound, compound 1, synthesized from actinomycetes, to develop an antimicrobial drug delivery material, CS-1, designated for the administration of compound 2 (CS-1@2), which exhibits pH-responsive antimicrobial effects. The physicochemical properties, in vitro biological characteristics, and bioactivity of CS-1@2 were rigorously evaluated. Results indicated that CS-1 possesses a porous structure, facilitating accelerated release of compound 2 in mildly acidic conditions. In vitro cellular assays were conducted, establishing a CHF model using doxorubicin-induced AC16 cardiomyocytes. This study aims to elucidate the mechanisms through which CS-1@2 mitigates doxorubicin-induced damage in AC16 myocardial cells, highlighting its potential in CHF management. This study lays a promising foundation for targeted therapy of chronic heart failure (CHF) and promotes its translational application in personalized cardiovascular medicine.

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以多糖为载体的载药复合材料减轻心肌细胞损伤

心力衰竭是心血管疾病患者死亡的主要原因，主要是慢性心力衰竭（CHF）和心肌组织损伤与细胞凋亡相关的结果。达格列净是一种SGLT-2抑制剂，以减少葡萄糖重吸收和预防心血管疾病而闻名，利用其药理学上的成功，我们设计并合成了一种新的衍生物，化合物2，以提高治疗效果。此外，我们以壳聚糖（CS）为载体基质，整合从放线菌中合成的生物活性化合物化合物1，开发了一种抗菌药物递送材料CS-1，用于给药化合物2 (CS-1@2)，该材料具有ph响应性的抗菌作用。对CS-1@2的理化性质、体外生物学特性和生物活性进行了严格的评价。结果表明，CS-1具有多孔结构，有利于化合物2在弱酸性条件下的加速释放。体外细胞检测，用阿霉素诱导的AC16心肌细胞建立CHF模型。本研究旨在阐明CS-1@2减轻阿霉素诱导的AC16心肌细胞损伤的机制，强调其在CHF治疗中的潜力。本研究为慢性心力衰竭（CHF）的靶向治疗奠定了良好的基础，促进了其在个体化心血管医学中的转化应用。

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来源期刊

Carbohydrate Research 化学-生化与分子生物学

CiteScore

5.00

自引率

3.20%

发文量

183

审稿时长

3.6 weeks

期刊介绍： Carbohydrate Research publishes reports of original research in the following areas of carbohydrate science: action of enzymes, analytical chemistry, biochemistry (biosynthesis, degradation, structural and functional biochemistry, conformation, molecular recognition, enzyme mechanisms, carbohydrate-processing enzymes, including glycosidases and glycosyltransferases), chemical synthesis, isolation of natural products, physicochemical studies, reactions and their mechanisms, the study of structures and stereochemistry, and technological aspects. Papers on polysaccharides should have a "molecular" component; that is a paper on new or modified polysaccharides should include structural information and characterization in addition to the usual studies of rheological properties and the like. A paper on a new, naturally occurring polysaccharide should include structural information, defining monosaccharide components and linkage sequence. Papers devoted wholly or partly to X-ray crystallographic studies, or to computational aspects (molecular mechanics or molecular orbital calculations, simulations via molecular dynamics), will be considered if they meet certain criteria. For computational papers the requirements are that the methods used be specified in sufficient detail to permit replication of the results, and that the conclusions be shown to have relevance to experimental observations - the authors'' own data or data from the literature. Specific directions for the presentation of X-ray data are given below under Results and "discussion".