Targeted drug delivery to selective cell has emerged as one of the most significant areas of biomedical engineering research today, so to optimize the therapeutic efficacy of a drug by localizing strictly its pharmacological action to a pathophysiologically relevant tissue system. The current study is aimed to develop saccharide conjugates for targeted delivery of metoprolol, the cardio-selective β-blocker. The examination was done in two significant steps. The initial step includes synthesis of modified saccharides (MS). These MS were used for synthesis of metoprolol-modified saccharide conjugates (MET-MS). The chemical modification of saccharides was evaluated for its swellability and HLB followed by FTIR and DSC. The affirmation of conjugate synthesis was finished by melting point and TLC as primary parameters followed by HR-MS, FTIR, DSC, and [1] H NMR study. Drug release analysis and cellular uptake study examination were completed utilizing H9c2 cell lines. Brine shrimp lethality bioassay was done to research the cytotoxicity of synthesized conjugates. The rate lethality and LC₅₀ values were dictated by contrasting the mean enduring hatchlings of the test and control tubes. In silico examination was performed to evaluate the possible binding of the developed conjugates with the GLUT-4. Homology model of the GLUT-4 was created utilizing SWISS MODEL server.

Graphical Abstract

中文翻译：

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用于心血管靶向的美托洛尔修饰的糖缀合物的合成、表征、计算机分析和药理学评价

靶向药物递送至选择性细胞已成为当今生物医学工程研究最重要的领域之一，因此通过将药物的药理作用严格定位于病理生理学相关的组织系统来优化药物的治疗效果。目前的研究旨在开发用于靶向递送美托洛尔（心脏选择性β-受体阻滞剂）的糖缀合物。检查分两个重要步骤进行。初始步骤包括合成修饰的糖类 (MS)。这些 MS 用于合成美托洛尔修饰的糖缀合物 (MET-MS)。用 FTIR 和 DSC 评估了糖类的化学改性的溶胀性和 HLB。以熔点和TLC为主要参数，然后HR-MS、FTIR、DSC、和 [1] H NMR 研究。利用H9c2细胞系完成药物释放分析和细胞摄取研究检查。进行盐水虾致死生物测定以研究合成缀合物的细胞毒性。致死率和LC_{50 个}值是通过对比测试管和对照管的平均持久孵化量来确定的。进行了计算机模拟检查以评估开发的缀合物与 GLUT-4 的可能结合。GLUT-4 的同源模型是利用 SWISS MODEL 服务器创建的。

图形概要