International Journal of Nanomedicine (Dec 2022)

ECM Mimicking Biodegradable Nanofibrous Scaffold Enriched with Curcumin/ZnO to Accelerate Diabetic Wound Healing via Multifunctional Bioactivity

  • Yadav S,
  • Arya DK,
  • Pandey P,
  • Anand S,
  • Gautam AK,
  • Ranjan S,
  • Saraf SA,
  • Mahalingam Rajamanickam V,
  • Singh S,
  • Chidambaram K,
  • Alqahtani T,
  • Rajinikanth PS

Journal volume & issue
Vol. Volume 17
pp. 6843 – 6859

Abstract

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Sachin Yadav,1,* Dilip Kumar Arya,1,* Prashant Pandey,1 Sneha Anand,1 Anurag Kumar Gautam,1 Shivendu Ranjan,2 Shubhini A Saraf,1 Vijayakumar Mahalingam Rajamanickam,1 Sanjay Singh,1 Kumarappan Chidambaram,3 Taha Alqahtani,3 Paruvathanahalli Siddalingam Rajinikanth1,4 1Department of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University, Lucknow, India; 2School of Nano Science and Technology, Indian Institute of Technology Kharagpur, Kharagpur, West Bengal, India; 3Department of Pharmacology and Toxicology, King Khalid University, Abha, Saudi Arabia; 4Department of Pharmaceutical Technology, School of Pharmacy, Taylor’s University Lakeside Campus, Kuala Lumpur Malaysia*These authors contributed equally to this workCorrespondence: Paruvathanahalli Siddalingam Rajinikanth, Department of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University, Lucknow, 226025, India, Email [email protected]: Foot ulceration is one of the most severe and debilitating complications of diabetes, which leads to the cause of non-traumatic lower-extremity amputation in 15– 24% of affected individuals. The healing of diabetic foot (DF) is a significant therapeutic problem due to complications from the multifactorial healing process. Electrospun nanofibrous scaffold loaded with various wound dressing materials has excellent wound healing properties due to its multifunctional action.Purpose: This work aimed to develop and characterize chitosan (CS)-polyvinyl alcohol (PVA) blended electrospun multifunctional nanofiber loaded with curcumin (CUR) and zinc oxide (ZnO) to accelerate diabetic wound healing in STZ-induced diabetic rats.Results: In-vitro characterization results revealed that nanofiber was fabricated successfully using the electrospinning technique. SEM results confirmed the smooth surface with web-like fiber nanostructure diameter ranging from 200 – 250 nm. An in-vitro release study confirmed the sustained release of CUR and ZnO for a prolonged time. In-vitro cell-line studies demonstrated significantly low cytotoxicity of nanofiber in HaCaT cells. Anti-bacterial studies demonstrated good anti-bacterial and anti-biofilm activities of nanofiber. In-vivo animal studies demonstrated an excellent wound-healing efficiency of the nanofibers in STZ–induced diabetic rats. Furthermore, the ELISA assay revealed that the optimized nanofiber membrane terminated the inflammatory phases successfully by downregulating the pro-inflammatory cytokines (TNF-α, MMP-2, and MMP-9) in wound healing. In-vitro and in-vivo studies conclude that the developed nanofiber loaded with bioactive material can promote diabetic wound healing efficiently via multifunction action such as the sustained release of bioactive molecules for a prolonged time of duration, proving anti-bacterial/anti-biofilm properties and acceleration of cell migration and proliferation process during the wound healing.Discussion: CUR-ZnO electrospun nanofibers could be a promising drug delivery platform with the potential to be scaled up to treat diabetic foot ulcers effectively.Graphical Abstract: Keywords: electrospinning, curcumin, zinc oxide, chitosan, polyvinyl alcohol, diabetic wound healing

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