{"title":"Repurposing Esmolol for Diabetic Wound Healing: Formulation Development, In-Silico and In-Vivo Evaluation in Diabetic Rats","authors":"Rahul Padalkar, Ashwini Madgulkar, Sudhir Kulkarni, Rutuja Sultanpure, Shrawani Nighot, Shreyas Barde","doi":"10.1007/s12247-025-10085-6","DOIUrl":null,"url":null,"abstract":"<div><p>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.</p><h3>Graphical Abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":656,"journal":{"name":"Journal of Pharmaceutical Innovation","volume":"20 5","pages":""},"PeriodicalIF":2.7000,"publicationDate":"2025-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Pharmaceutical Innovation","FirstCategoryId":"3","ListUrlMain":"https://link.springer.com/article/10.1007/s12247-025-10085-6","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0
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.
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.