Repurposing Esmolol for Diabetic Wound Healing: Formulation Development, In-Silico and In-Vivo Evaluation in Diabetic Rats

IF 2.7 4区 医学 Q2 PHARMACOLOGY & PHARMACY
Rahul Padalkar, Ashwini Madgulkar, Sudhir Kulkarni, Rutuja Sultanpure, Shrawani Nighot, Shreyas Barde
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Abstract

Diabetic wounds are challenging to heal due to multiple pathologies in the wound healing process. The complex cellular environment surrounding diabetic wounds impairs the functioning of vital cells, including vascular endothelial cells, fibroblasts, and epithelial cells, which are essential for wound healing, thereby hindering the repair process. The present work demonstrates the potential of esmolol hydrochloride in diabetic wound healing through molecular docking studies and hydrogel formulation along with D-panthenol. Esmolol hydrochloride exhibited significant binding affinity withCaspase-8, MMP1 and MMP8. Esmolol hydrochloride did not show any cytotoxic effect in the MTT assay at concentrations up to 250uM. Based upon these observations, esmolol(14%) was formulated into a hydrogel (WHG) along with D-panthenol (5%). The formulation was evaluated for wound healing activity in streptozotocin-induced diabetic rats through the excision wound model. The WHG group showed almost 96% wound closure at the end of 21 days. At various times during this study period, wound tissues were examined for histopathological changes. Cell proliferation, remodeling and collagen building observed in the WHG group suggested excellent progress of wound healing. A considerable increase in hydroxyproline and hexosamine levels was also observed during the study period, indicating collagen and extracellular matrix synthesis. The combination index value of 1.02 indicated additive effect of both the actives in wound healing. These findings suggest that esmolol and D-panthenol hydrogel can serve as a promising approach for diabetic wound healing.

Graphical Abstract

Abstract Image

艾司洛尔用于糖尿病伤口愈合:糖尿病大鼠的配方开发、计算机和体内评估
由于糖尿病创面在愈合过程中存在多种病理因素,创面愈合具有挑战性。糖尿病伤口周围复杂的细胞环境损害了重要细胞的功能,包括血管内皮细胞、成纤维细胞和上皮细胞,这些细胞对伤口愈合至关重要,从而阻碍了修复过程。本研究通过分子对接研究和与d -泛醇的水凝胶配方证明了盐酸艾司洛尔在糖尿病伤口愈合中的潜力。盐酸艾司洛尔与caspase -8、MMP1和MMP8具有显著的结合亲和力。盐酸艾斯洛尔在浓度高达250uM的MTT试验中未显示出任何细胞毒性作用。根据这些观察结果,艾司洛尔(14%)与d -泛醇(5%)一起配制成水凝胶(WHG)。通过创面切除模型评价该制剂对链脲佐菌素诱导的糖尿病大鼠创面愈合活性。WHG组在21 d时伤口愈合率接近96%。在研究期间的不同时间,对伤口组织进行了组织病理学检查。WHG组的细胞增殖、重塑和胶原蛋白的形成提示伤口愈合进展良好。在研究期间还观察到羟基脯氨酸和己糖胺水平的显著增加,表明胶原蛋白和细胞外基质的合成。联合指数为1.02,表明两种活性物质在创面愈合中的加性作用。这些发现表明,艾司洛尔和d -泛醇水凝胶可以作为一种有前途的方法用于糖尿病伤口愈合。图形抽象
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来源期刊
Journal of Pharmaceutical Innovation
Journal of Pharmaceutical Innovation PHARMACOLOGY & PHARMACY-
CiteScore
3.70
自引率
3.80%
发文量
90
审稿时长
>12 weeks
期刊介绍: The Journal of Pharmaceutical Innovation (JPI), is an international, multidisciplinary peer-reviewed scientific journal dedicated to publishing high quality papers emphasizing innovative research and applied technologies within the pharmaceutical and biotechnology industries. JPI''s goal is to be the premier communication vehicle for the critical body of knowledge that is needed for scientific evolution and technical innovation, from R&D to market. Topics will fall under the following categories: Materials science, Product design, Process design, optimization, automation and control, Facilities; Information management, Regulatory policy and strategy, Supply chain developments , Education and professional development, Journal of Pharmaceutical Innovation publishes four issues a year.
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