Design, Development, and Characterization of Ellagic Acid-Loaded Transethosomal Gel Using 23 Factorial Design Approach for the Management of Diabetic Foot Ulcer - Research

Aug 28, 2026

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Diabetic foot ulcers (DFUs) are a debilitating complication of diabetes, driven by oxidative stress, inflammation, and insufficient therapeutic penetration that often culminates in chronic infection and amputation. 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.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages24

Reading Time1 h 0 min

AccessFree to download

Abstract

Highlights

Keywords and Abbreviations

Introduction

Epidemiology and burden of DFUs

Pathophysiology and treatment challenges

Classification and unmet clinical needs

Materials and Methods

Results and Discussion

Conclusion

BioNanoScience (2026) 16:133 [https://doi.org/10.1007/s12668-025-02380-w](https://doi.org/10.1007/s12668-025-02380-w) RESEARCH Design, Development, and Characterization of Ellagic Acid-Loaded Transethosomal Gel Using 23 Factorial Design Approach for the Management of Diabetic Foot Ulcer Sanskriti Sarkar1 · Amarjitsing Rajput2 · Santosh Butle3 · Pankaj Jain4 · Shailesh S. Chalikwar4 Received: 4 October 2025 / Accepted: 22 December 2025 / Published online: 16 January 2026 © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2026 Abstract Diabetic 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. Sanskriti Sarkar and Amarjitsing Rajput contributed equally to this work. 􀀍 Shailesh S. Chalikwar[pharmashailesh@rediffmail.com](pharmashailesh@rediffmail.com) 1 R. C. Patel Institute of Pharmacy, Karwand Naka, Shirpur, Maharashtra 425405, India 2 Department of Pharmaceutics, Poona College of Pharmacy, Bharati Vidyapeeth (Deemed to be University), Pune, Maharashtra 411038, India 3 School of Pharmacy, Department of Pharmaceutical Chemistry, S.R.T.M. University, Nanded, Maharashtra 431606, India 4 Department of Industrial Pharmacy & Quality Assurance, R. C. Patel Institute of Pharmaceutical Education & Research, Karwand Naka, Shirpur, Dist-Dhule, Maharashtra 425405, India Graphical Abstract Highlights ● Transethosomal gel formulation enriched with ellagic acid for the treatment of diabetic foot ulcers (DFUs) were formulated. ● Optimized formulation exhibited ideal physicochemical characteristics. ● Stability evaluations suggested a shelf life of 27.41 months under refrigerated conditions and 21.83 months at ambient conditions. ● The developed transethosomal gel system signifies a promising advanced delivery for managing DFUs. Keywords Diabetic foot ulcer · Ellagic acid · Transethosomes · Gel · Wound healing · Dermatokinetics Abbreviations Term Full Form % Percent °C Degree Celsius ATR-IR Attenuated Total Reflectance-Fourier Transform Infrared Spectroscopy DFU Diabetic Foot Ulcer DLS Dynamic Light Scattering DM Diabetes Mellitus DSC Differential Scanning Calorimetry EA Ellagic Acid EE Entrapment Efficiency ET Ethanol h Hour HPLC High-Performance Liquid Chromatography IL Interleukin min Minute nm Nanometer PBS Phosphate Buffered Saline PDI Polydispersity Index pH Potential of Hydrogen PL90G Phospholipon 90GROS Reactive Oxygen Species rpm

FAQs

What problem does the ellagic acid-loaded transethosomal gel target in diabetic foot ulcers?

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.

How was the transethosomal gel formulation optimized?

Transethosomes were prepared using cold ethanol injection and optimized with a 2³ factorial design, then incorporated into Carbopol 940 gel for the final formulation.

What preclinical evidence supports the gel’s effectiveness?

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.

Aug 28, 2026

Upload by Oliver