International Journal of Nanomedicine (Dec 2024)

Enhancing Photothermal Therapy for Antibiofilm Wound Healing: Insights from Graphene Oxide-Cranberry Nanosheet Loaded Hydrogel in vitro, in silico, and in vivo Evaluation

  • Elhabal SF,
  • Al-Zuhairy SAS,
  • El-Nabarawi M,
  • Mohamed Elrefai MF,
  • Shoela MS,
  • Hababeh S,
  • Nelson J,
  • Abdel Khalek MA,
  • Fady M,
  • Elzohairy NA,
  • Amin ME,
  • Khamis GM,
  • Rizk A,
  • Ahmed SM,
  • El-Rashedy AA,
  • Mohany M,
  • Al-Roujayee AS,
  • Faheem AM,
  • Amin A

Journal volume & issue
Vol. Volume 19
pp. 12999 – 13027

Abstract

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Sammar Fathy Elhabal,1 Saeed AS Al-Zuhairy,2 Mohamed El-Nabarawi,3 Mohamed Fathi Mohamed Elrefai,4,5 Mai S Shoela,6 Sandra Hababeh,7 Jakline Nelson,8 Mohamed A Abdel Khalek,9 Marwa Fady,10,11 Nahla A Elzohairy,11,12 Mariam E Amin,13 Gehad M Khamis,6 Amira Rizk,14 Sara Mohamed Ahmed,15 Ahmed A El-Rashedy,16 Mohamed Mohany,17 Abdulaziz S Al-Roujayee,18 Ahmed Mohsen Faheem,19 Amr Amin20 1Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Modern University for Technology and Information (MTI), Mokattam, Cairo, Egypt; 2Department of Pharmacy, Kut University College, Kut, Wasit, Iraq; 3Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, Egypt; 4Department of Anatomy, physiology and Biochemistry, Faculty of Medicine, the Hashemite University, Zarqa, Jordan; 5Department of Anatomy and Embryology, Faculty of Medicine, Ain Shams University, Cairo, Egypt; 6Department of Clinical Pharmacology, Faculty of Medicine, Alexandria University, Alexandria, Egypt; 7Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia; 8Department of Microbiology and Immunology, Faculty of Pharmacy, Nahda University, Beni-Suef, Egypt; 9Institute of Nanoscience and Nanotechnology, Kafrelsheikh University, Kafrelsheikh, 33516, Egypt; 10Zagazig University Hospitals, Infection Control Unit, Zagazig, 44519, Egypt; 11Modern University for Technology & Information, Department of Microbiology and Immunology, Pharmacy College., Cairo Governorat, Egypt; 12Air Force Specialized Hospital, Cairo, Egypt; 13Microbiology and Immunology Department, Faculty of Pharmacy, Suez Canal University, Ismailia, Egypt; 14Food Science and technology, Department Faculty of Agricultural, Tanta University, Tanta, Egypt; 15Department of Pharmaceutics, College of Pharmaceutical Sciences and Drug Manufacturing, Misr University for Science and Technology, Giza, 12585, Egypt; 16Chemistry of Natural and Microbial Products Department, National Research Center (NRC), Giza, Egypt; 17Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia; 18Department of Dermatology and Venereology, College of Medicine, Al Imam Mohammad Ibn Saud Islamic University, Riyadh, Saudi Arabia; 19Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Mansoura University, Mansoura, Egypt; 20College of Medicine, Sharjah University, Sharjah, United Arab EmiratesCorrespondence: Sammar Fathy Elhabal; Amr Amin, Email [email protected], [email protected]; [email protected]: Diabetic foot ulcers present a formidable challenge due to colonization by biofilm-forming microorganisms, heightened oxidative stress, and continuous wound maceration caused by excessive exudation.Methods: To address these issues, we developed a robust, stretchable, electro-conductive, self-healing, antioxidant, and antibiofilm hydrogel. This hydrogel was synthesized through the crosslinking of polyvinyl alcohol (PVA) and chitosan (CH) with boric acid. To enhance its antimicrobial efficacy, graphene oxide (GO), produced via electrochemical exfoliation in a zinc ion-based electrolyte medium, was incorporated. For optimal antibiofilm performance, GO was functionalized with cranberry (CR) phenolic extracts, forming a graphene oxide-cranberry nanohybrid (GO-CR).Results: The incorporation of GO-CR into the hydrogel significantly improved its stretchability (280% for PVA/CH/GO-CR compared to 200% for PVA/CH). Additionally, the hydrogel demonstrated efficient photothermal conversion under near-infrared (NIR) light, enabling dynamic exudate removal, which is expected to minimize retained exudate between the wound and the dressing, reducing the risk of wound maceration. The hydrogel effectively reduced levels of lipopolysaccharide (LPS)-induced skin inflammation markers, significantly lowering the expression of NLRP3, TNF-α, IL-6, and IL-1β by 39.2%, 31.9%, 41%, and 52.3%, respectively. Histopathological and immunohistochemical analyses further confirmed reduced inflammation and enhanced wound healing.Conclusion: The PVA/CH/GO-CR hydrogel exhibits multifunctional properties that enhance wound healing ulcers. Its superior mechanical, antibacterial, and anti-inflammatory properties and ability to promote angiogenesis make it a promising candidate for effective wound management in diabetic patients. Keywords: antibiofilm, cranberry extract, electro conductive hydrogel, graphene oxide, nanocomposite, photothermal conversion, self-healing, wound healing

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