Abstract
Glutathione (GSH) is an anti-inflammatory and antioxidant biomolecule. Polycaprolactone (PCL) nanofiber mesh (NFM) is capable of the attachment and release of biomolecules for prolonged periods and has the potential as a transdermal drug delivery system during wound healing for a diabetic patient. Our earlier study found that high levels of sugar in diabetic male mice were significantly decreased by daily doses of glutathione administered on the mice. Furthermore, oxidative stress found in diabetic male mice led to the total depletion of glutathione levels in the body’s organs (pancreas, spleen, epididymis, and testis). The objective of this study was to attach GSH with PCL NFM for the controlled release of GSH biomolecules for long periods of time from the fiber mesh into a diabetic body. This study produced PCL NFM using an electrospun technique and tested it on mice to evaluate its efficiency as a dermal drug delivery mechanism. This study dissolved GSH (2.5 mg/mL) with phosphate-buffered saline (PBS) and glutaraldehyde (GLU) solution to create GSH-PBS and GSH-GLU complexes. Each complex was used to soak PCL NFM for 24 h and dried to create PCL-GSH-PBS and PCL-GSH-GLU meshes. Fiber morphology, degradation, fibroblast cell proliferation, cytotoxicity, and GSH release activities from each mesh were compared. Fibroblast cell adhesion and cytotoxicity tests found excellent biocompatibility of both GSH-immobilized PCL meshes and no degradation until 20 days of the study period. The disk diffusion method was conducted to test the antibacterial properties of the sample groups. Release tests confirmed that the attachment of GSH with PCL by GSH-GLU complex resulted in a steady release of GSH compared to the fast release of GSH from PCL-GSH-PBS mesh. The disk diffusion test confirmed that PCL-GSH-GLU has antibacterial properties. The above results conclude that GSH-GLU immobilized PCL NFM can be a suitable candidate for a transdermal anti-oxidative and anti-bacterial drug delivery system such as bandage, skin graft for wound healing application in a diabetic patient.
Highlights
IntroductionDiabetics have high levels of reactive oxygen species (ROS) and not enough antioxidants to neutralize them [1]
We have developed an electrospun nanofiber membrane nanofiber mesh (NFM) that can be used as a drug delivery system
Superoxide anions in the body are during direct oxygen reduction when electrons leak from the electron transfer chain and produced during direct oxygen reduction when electrons leak from the electron transfer oxidative phosphorylation processes in mitochondria [19]
Summary
Diabetics have high levels of reactive oxygen species (ROS) and not enough antioxidants to neutralize them [1]. Diabetics have low levels of intracellular glutathione [2]. Enzymatic glutathione redox systems, such as glutathione (GSH), glutathione reductase (GR), and glutathione peroxidase (Gpx), can neutralize excess ROS and maintain a proper cellular environment [3]. Free radicals are formed disproportionately in diabetes; abnormally high levels of free radicals and the simultaneous decline of antioxidant defense mechanisms can lead to the development of insulin resistance [4]. These consequences of oxidative stress can promote the development of complications such as diabetes mellitus [5]
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