Naringenin Loaded Hydrogel Supports Wound Repair in a Cell Model of Diabetic Skin

Mandeep Marwah; Yukta Sameer Hindalekar; Karan Rana; Hala Shokr; Mohamad Anas Al Tahan; Lissette Sanchez Aranguren; Maymunah  Sarr; Rosie Kainth; Parmida Babaei; Humaa  Asif; Shakil Ahmad; Anisa Mahomed

doi:10.1007/s11095-026-04029-z

Naringenin Loaded Hydrogel Supports Wound Repair in a Cell Model of Diabetic Skin

Mandeep Marwah^*, Yukta Sameer Hindalekar, Karan Rana, Hala Shokr, Mohamad Anas Al Tahan, Lissette Sanchez Aranguren, Maymunah Sarr, Rosie Kainth, Parmida Babaei, Humaa Asif , Shakil Ahmad, Anisa Mahomed^*

^*Corresponding author for this work

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Abstract

Introduction: Diabetic foot ulcers are a major complication of diabetes, driven by inflammation, oxidative stress, and poor vascular function. Naringenin, a citrus flavonoid, addresses these factors but has low solubility and stability. We developed a Na-AMPS hydrogel dressing to enhance its delivery under diabetic-like conditions. Methods: A Na-AMPS hydrogel containing 0.02%(w/w) naringenin was formulated and assessed for rheological and adhesive properties, drug release, and biological activity in HUVEC and HDFa cells. Cytotoxicity (XTT), reactive oxygen species (ROS), mitochondrial membrane potential (TMRM), cytokine levels (IL-6, IL-8, MMP-9, TGF-β), and wound closure (scratch assay) were measured. Results/Discussion: Naringenin modestly reduced the hydrogel elastic modulus (15,791.5 ± 1965 Pa at 30 Hz) without affecting adhesion. Release studies showed rapid drug release from solution but sustained release from hydrogels (17.88 ± 2.61% over 24 h). Under hyperglycaemic and pro-inflammatory conditions, naringenin significantly decreased ROS in HUVECs (41,030.58 ± 2737 to 31,778.74 ± 1822 AU; p < 0.001) and HDFa cells (38,188.13 ± 4593 to 29,950.94 ± 1426 AU; p < 0.05). Naringenin improved mitochondrial membrane potential in both cell types (p < 0.05–0.01) and attenuated pro-inflammatory cytokines. IL-6 decreased in HUVECs (39.40 ± 5.02 to 27.15 ± 3.10 pg/mL; p < 0.01) and HDFa cells (40.05 ± 2.23 to 16.41 ± 1.27 pg/mL; p < 0.0001). In HDFa’s, MMP-9 was reduced (403.43 ± 18.70 to 195.33 ± 11.02 pg/mL; p < 0.0001), while in HUVECs, wound closure was enhanced. Conclusion: Naringenin-loaded Na-AMPS hydrogels demonstrated sustained release, suitable mechanical properties, and significant antioxidant, anti-inflammatory, and wound healing effects. These findings highlight their therapeutic potential for diabetic wounds treatment.

Original language	English
Number of pages	15
Journal	Pharmaceutical Research
Early online date	31 Jan 2026
DOIs	https://doi.org/10.1007/s11095-026-04029-z
Publication status	E-pub ahead of print - 31 Jan 2026

Bibliographical note

Copyright © The Author(s). This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit https://creativecommons.org/licenses/by/4.0/.

Data Access Statement

The datasets generated and/or analysed during the current study are not publicly available due to ongoing related studies but are available from the corresponding author on reasonable request.

Funding

This research was funded by Breakthrough T1D UK (Small Grant Award grant number- 1-SGA-2024–0002) awarded to M.K.M.

Keywords

Controlled-release
Diabetic wound healing
Hydrogel
Inflammation
Naringenin biological activity
Topical drug delivery

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10.1007/s11095-026-04029-zLicence: CC BY 4.0

Naringenin Loaded Hydrogel Supports Wound Repair in a Cell Model of Diabetic Skin
Copyright © The Author(s). This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit https://creativecommons.org/licenses/by/4.0/.
Final published version, 2 MBLicence: CC BY 4.0

Cite this

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title = "Naringenin Loaded Hydrogel Supports Wound Repair in a Cell Model of Diabetic Skin",

abstract = "Introduction: Diabetic foot ulcers are a major complication of diabetes, driven by inflammation, oxidative stress, and poor vascular function. Naringenin, a citrus flavonoid, addresses these factors but has low solubility and stability. We developed a Na-AMPS hydrogel dressing to enhance its delivery under diabetic-like conditions. Methods: A Na-AMPS hydrogel containing 0.02%(w/w) naringenin was formulated and assessed for rheological and adhesive properties, drug release, and biological activity in HUVEC and HDFa cells. Cytotoxicity (XTT), reactive oxygen species (ROS), mitochondrial membrane potential (TMRM), cytokine levels (IL-6, IL-8, MMP-9, TGF-β), and wound closure (scratch assay) were measured. Results/Discussion: Naringenin modestly reduced the hydrogel elastic modulus (15,791.5 ± 1965 Pa at 30 Hz) without affecting adhesion. Release studies showed rapid drug release from solution but sustained release from hydrogels (17.88 ± 2.61% over 24 h). Under hyperglycaemic and pro-inflammatory conditions, naringenin significantly decreased ROS in HUVECs (41,030.58 ± 2737 to 31,778.74 ± 1822 AU; p < 0.001) and HDFa cells (38,188.13 ± 4593 to 29,950.94 ± 1426 AU; p < 0.05). Naringenin improved mitochondrial membrane potential in both cell types (p < 0.05–0.01) and attenuated pro-inflammatory cytokines. IL-6 decreased in HUVECs (39.40 ± 5.02 to 27.15 ± 3.10 pg/mL; p < 0.01) and HDFa cells (40.05 ± 2.23 to 16.41 ± 1.27 pg/mL; p < 0.0001). In HDFa{\textquoteright}s, MMP-9 was reduced (403.43 ± 18.70 to 195.33 ± 11.02 pg/mL; p < 0.0001), while in HUVECs, wound closure was enhanced. Conclusion: Naringenin-loaded Na-AMPS hydrogels demonstrated sustained release, suitable mechanical properties, and significant antioxidant, anti-inflammatory, and wound healing effects. These findings highlight their therapeutic potential for diabetic wounds treatment.",

keywords = "Controlled-release, Diabetic wound healing, Hydrogel, Inflammation, Naringenin biological activity, Topical drug delivery",

author = "Mandeep Marwah and Hindalekar, {Yukta Sameer} and Karan Rana and Hala Shokr and {Al Tahan}, {Mohamad Anas} and {Sanchez Aranguren}, Lissette and Maymunah Sarr and Rosie Kainth and Parmida Babaei and Humaa Asif and Shakil Ahmad and Anisa Mahomed",

note = "Copyright {\textcopyright} The Author(s). This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit https://creativecommons.org/licenses/by/4.0/.",

year = "2026",

month = jan,

day = "31",

doi = "10.1007/s11095-026-04029-z",

language = "English",

journal = "Pharmaceutical Research ",

issn = "0724-8741",

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TY - JOUR

T1 - Naringenin Loaded Hydrogel Supports Wound Repair in a Cell Model of Diabetic Skin

AU - Marwah, Mandeep

AU - Hindalekar, Yukta Sameer

AU - Rana, Karan

AU - Shokr, Hala

AU - Al Tahan, Mohamad Anas

AU - Sanchez Aranguren, Lissette

AU - Sarr, Maymunah

AU - Kainth, Rosie

AU - Babaei, Parmida

AU - Asif , Humaa

AU - Ahmad, Shakil

AU - Mahomed, Anisa

N1 - Copyright © The Author(s). This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit https://creativecommons.org/licenses/by/4.0/.

PY - 2026/1/31

Y1 - 2026/1/31

N2 - Introduction: Diabetic foot ulcers are a major complication of diabetes, driven by inflammation, oxidative stress, and poor vascular function. Naringenin, a citrus flavonoid, addresses these factors but has low solubility and stability. We developed a Na-AMPS hydrogel dressing to enhance its delivery under diabetic-like conditions. Methods: A Na-AMPS hydrogel containing 0.02%(w/w) naringenin was formulated and assessed for rheological and adhesive properties, drug release, and biological activity in HUVEC and HDFa cells. Cytotoxicity (XTT), reactive oxygen species (ROS), mitochondrial membrane potential (TMRM), cytokine levels (IL-6, IL-8, MMP-9, TGF-β), and wound closure (scratch assay) were measured. Results/Discussion: Naringenin modestly reduced the hydrogel elastic modulus (15,791.5 ± 1965 Pa at 30 Hz) without affecting adhesion. Release studies showed rapid drug release from solution but sustained release from hydrogels (17.88 ± 2.61% over 24 h). Under hyperglycaemic and pro-inflammatory conditions, naringenin significantly decreased ROS in HUVECs (41,030.58 ± 2737 to 31,778.74 ± 1822 AU; p < 0.001) and HDFa cells (38,188.13 ± 4593 to 29,950.94 ± 1426 AU; p < 0.05). Naringenin improved mitochondrial membrane potential in both cell types (p < 0.05–0.01) and attenuated pro-inflammatory cytokines. IL-6 decreased in HUVECs (39.40 ± 5.02 to 27.15 ± 3.10 pg/mL; p < 0.01) and HDFa cells (40.05 ± 2.23 to 16.41 ± 1.27 pg/mL; p < 0.0001). In HDFa’s, MMP-9 was reduced (403.43 ± 18.70 to 195.33 ± 11.02 pg/mL; p < 0.0001), while in HUVECs, wound closure was enhanced. Conclusion: Naringenin-loaded Na-AMPS hydrogels demonstrated sustained release, suitable mechanical properties, and significant antioxidant, anti-inflammatory, and wound healing effects. These findings highlight their therapeutic potential for diabetic wounds treatment.

AB - Introduction: Diabetic foot ulcers are a major complication of diabetes, driven by inflammation, oxidative stress, and poor vascular function. Naringenin, a citrus flavonoid, addresses these factors but has low solubility and stability. We developed a Na-AMPS hydrogel dressing to enhance its delivery under diabetic-like conditions. Methods: A Na-AMPS hydrogel containing 0.02%(w/w) naringenin was formulated and assessed for rheological and adhesive properties, drug release, and biological activity in HUVEC and HDFa cells. Cytotoxicity (XTT), reactive oxygen species (ROS), mitochondrial membrane potential (TMRM), cytokine levels (IL-6, IL-8, MMP-9, TGF-β), and wound closure (scratch assay) were measured. Results/Discussion: Naringenin modestly reduced the hydrogel elastic modulus (15,791.5 ± 1965 Pa at 30 Hz) without affecting adhesion. Release studies showed rapid drug release from solution but sustained release from hydrogels (17.88 ± 2.61% over 24 h). Under hyperglycaemic and pro-inflammatory conditions, naringenin significantly decreased ROS in HUVECs (41,030.58 ± 2737 to 31,778.74 ± 1822 AU; p < 0.001) and HDFa cells (38,188.13 ± 4593 to 29,950.94 ± 1426 AU; p < 0.05). Naringenin improved mitochondrial membrane potential in both cell types (p < 0.05–0.01) and attenuated pro-inflammatory cytokines. IL-6 decreased in HUVECs (39.40 ± 5.02 to 27.15 ± 3.10 pg/mL; p < 0.01) and HDFa cells (40.05 ± 2.23 to 16.41 ± 1.27 pg/mL; p < 0.0001). In HDFa’s, MMP-9 was reduced (403.43 ± 18.70 to 195.33 ± 11.02 pg/mL; p < 0.0001), while in HUVECs, wound closure was enhanced. Conclusion: Naringenin-loaded Na-AMPS hydrogels demonstrated sustained release, suitable mechanical properties, and significant antioxidant, anti-inflammatory, and wound healing effects. These findings highlight their therapeutic potential for diabetic wounds treatment.

KW - Controlled-release

KW - Diabetic wound healing

KW - Hydrogel

KW - Inflammation

KW - Naringenin biological activity

KW - Topical drug delivery

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DO - 10.1007/s11095-026-04029-z

M3 - Article

SN - 0724-8741

JO - Pharmaceutical Research

JF - Pharmaceutical Research

ER -

Naringenin Loaded Hydrogel Supports Wound Repair in a Cell Model of Diabetic Skin

Abstract

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Data Access Statement

Funding

Keywords

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