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This work develops an optimized ellagic acid-loaded transethosomal gel to improve topical delivery and therapeutic performance. Transethosomes were produced by cold ethanol injection and optimized via a 2³ factorial design, then incorporated into Carbopol 940 gel. The optimized system showed nanoscale vesicles, high entrapment, sustained release, improved ex vivo permeation, and complete wound healing in streptozotocin-induced diabetic rats within 14 days.",{"@graph":69,"@context":123},[70,84,106],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/design-development-and-characterization-of-ellagic-acid-loaded-transethosomal-gel-using-23-factorial-design-approach-for-the-management-of-diabetic-foot-ulcer-research/156117/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/design-development-and-characterization-of-ellagic-acid-loaded-transethosomal-gel-using-23-factorial-design-approach-for-the-management-of-diabetic-foot-ulcer-research/156117.png","ImageObject",300,407,{"name":92,"@type":93},"Oliver","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-08","2026-08-28",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",18,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"What problem does the ellagic acid-loaded transethosomal gel target in diabetic foot ulcers?","Question",{"text":113,"@type":114},"It targets impaired wound healing caused by oxidative stress, inflammation, and poor skin penetration of therapeutics, aiming to improve topical delivery and therapeutic efficacy for DFUs.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"How was the transethosomal gel formulation optimized?",{"text":118,"@type":114},"Transethosomes were prepared using cold ethanol injection and optimized with a 2³ factorial design, then incorporated into Carbopol 940 gel for the final formulation.",{"name":120,"@type":111,"acceptedAnswer":121},"What preclinical evidence supports the gel’s effectiveness?",{"text":122,"@type":114},"In vitro release showed sustained delivery, ex vivo rat skin permeation demonstrated a much higher flux than conventional gel, and in vivo testing in streptozotocin-induced diabetic rats achieved complete wound healing within 14 days.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},156117,1787953904,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":140,"language":141,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":142,"faqs":143,"seo_title":144,"seo_description":67,"update_tm":130,"read_time":26},8796095461610,"https://ap-avatar.wpscdn.com/davatar_276721f389ce27ea32af1340a28f341c","BioNanoScience (2026) 16:133  \n[https://doi.org/10.1007/s12668-025-02380-w](https://doi.org/10.1007/s12668-025-02380-w)  \nRESEARCH  \nDesign, Development, and Characterization of Ellagic Acid-Loaded Transethosomal Gel Using 23 Factorial Design Approach for the Management of Diabetic Foot Ulcer  \nSanskriti Sarkar1 · Amarjitsing Rajput2 · Santosh Butle3 · Pankaj Jain4 · Shailesh S. Chalikwar4  \nReceived: 4 October 2025 / Accepted: 22 December 2025 / Published online: 16 January 2026  \n© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2026  \nAbstract  \nDiabetic foot ulcers (DFUs) are a debilitating complication of diabetes, characterized by impaired wound healing due to oxidative stress, inflammation, and poor tissue penetration of therapeutics, often resulting in chronic infections and amputations. Ellagic acid, a natural polyphenol with potent antioxidant, anti-inflammatory, and angiogenic properties, shows promise for DFU treatment but is limited by low solubility and skin permeability. This study aimed to develop an optimized ellagic acid-loaded transethosomal gel to enhance topical delivery and therapeutic efficacy. Transethosomes were prepared via cold ethanol injection, optimized using a 2³ factorial design, and incorporated into Carbopol 940 gel. The optimized formulation has a vesicle size of 191.5 ± 1.86 nm, PDI of 0.164, zeta potential of-32.5 ± 1.7 mV, and entrapment efficiency of 94.5 ± 0.94%. In vitro release demonstrated sustained drug delivery (82.95 ± 1.20% at 12 h) versus pure drug (68.34 ± 1.30%), while ex vivo permeation through rat skin showed an 11-fold higher flux (24.57 ± 0.52 µg/cm²/h) than conventional gel. In vivo evaluation in streptozotocin-induced diabetic rat models illustrated complete wound healing (Wagner Grade 0) within 14 days following EA-TRE gel treatment, demonstrating a markedly superior performance compared to traditional formulations. Thus, the developed transethosomal gel system signifies a promising advanced delivery platform integrating enhanced skin penetration, controlled release, and superior therapeutic efficacy for managing DFUs.  \nSanskriti Sarkar and Amarjitsing Rajput contributed equally to this work.  \n􀀍 Shailesh S. Chalikwar[pharmashailesh@rediffmail.com](pharmashailesh@rediffmail.com)  \n1 R. C. Patel Institute of Pharmacy, Karwand Naka, Shirpur, Maharashtra 425405, India  \n2 Department of Pharmaceutics, Poona College of Pharmacy, Bharati Vidyapeeth (Deemed to be University), Pune, Maharashtra 411038, India  \n3 School of Pharmacy, Department of Pharmaceutical Chemistry, S.R.T.M. University, Nanded, Maharashtra 431606, India  \n4 Department of Industrial Pharmacy & Quality Assurance, R.  \nC. Patel Institute of Pharmaceutical Education & Research, Karwand Naka, Shirpur, Dist-Dhule, Maharashtra 425405, India  \nGraphical Abstract  \nHighlights  \n● Transethosomal gel formulation enriched with ellagic acid for the treatment of diabetic foot ulcers (DFUs) were formulated.  \n● Optimized formulation exhibited ideal physicochemical characteristics.  \n● Stability evaluations suggested a shelf life of 27.41 months under refrigerated conditions and 21.83 months at ambient conditions.  \n● The developed transethosomal gel system signifies a promising advanced delivery for managing DFUs.  \nKeywords Diabetic foot ulcer · Ellagic acid · Transethosomes · Gel · Wound healing · Dermatokinetics  \nAbbreviations  \nTerm Full Form  \n% Percent  \n°C Degree Celsius  \nATR-IR Attenuated Total Reflectance-Fourier Transform  \nInfrared Spectroscopy  \nDFU Diabetic Foot Ulcer  \nDLS Dynamic Light Scattering  \nDM Diabetes Mellitus  \nDSC Differential Scanning Calorimetry  \nEA Ellagic Acid  \nEE Entrapment Efficiency  \nET Ethanol  \nh Hour  \nHPLC High-Performance Liquid Chromatography IL Interleukin  \nmin Minute  \nnm Nanometer  \nPBS Phosphate Buffered Saline PDI Polydispersity Index  \npH Potential of Hydrogen  \nPL90G Phospholipon 90GROS Reactive Oxygen Species rpm ","cbCainkMof8EgaDa","https://ap.wps.com/l/cbCainkMof8EgaDa","pdf",5455896,24,"English","# Abstract\n# Highlights\n# Keywords and Abbreviations\n# Introduction\n## Epidemiology and burden of DFUs\n## Pathophysiology and treatment challenges\n## Classification and unmet clinical needs\n# Materials and Methods\n# Results and Discussion\n# Conclusion","[{\"question\":\"What problem does the ellagic acid-loaded transethosomal gel target in diabetic foot ulcers?\",\"answer\":\"It targets impaired wound healing caused by oxidative stress, inflammation, and poor skin penetration of therapeutics, aiming to improve topical delivery and therapeutic efficacy for DFUs.\"},{\"question\":\"How was the transethosomal gel formulation optimized?\",\"answer\":\"Transethosomes were prepared using cold ethanol injection and optimized with a 2³ factorial design, then incorporated into Carbopol 940 gel for the final formulation.\"},{\"question\":\"What preclinical evidence supports the gel’s effectiveness?\",\"answer\":\"In vitro release showed sustained delivery, ex vivo rat skin permeation demonstrated a much higher flux than conventional gel, and in vivo testing in streptozotocin-induced diabetic rats achieved complete wound healing within 14 days.\"}]","Design, Development, and Characterization of Ellagic Acid-Loaded Transethosomal Gel Using 23 Factorial Design Approach for the Management of Diabetic Foot Ulcer - Research | PDF"]