Diabetic foot ulcers (DFU) are chronic wounds, which do not respond to traditional wound treatments. In this work, wound dressings of glibenclamide (GB) incorporated into a novel mixed matrix were fabricated in the aim of accelerating the healing process of diabetic wounds. GB was loaded into different weight ratios of Soluplus® (SP) and polyvinylpyrrolidone (PVP). The developed dressings were characterized İn vitro and in vivo, for their ability to promote diabetic wound healing. The particle size was between (1.4-2) µm. The morphology abided by the SP/PVP ratio in the formulated microparticles. Cup/bowl shape, semispherical with corrugated surface, apple shape with smooth surface, concave/star shape, and Irregular corrugated morphology were denoted for GB-SP/PVP1-0, GB-SP/PVP1-1, GB-SP/PVP0-1, GB-SP/PVP1-2, and GB-SP/PVP2-1 formulations, respectively. Glibenclamide was in amorphous form and hydrogen-bonded with the matrix polymers. The GB-SP/PVP0-1 wound dressings showed a burst drug release in about 1 hour due to the hydrophilic nature of PVP. The other GB-SP/PVP formulated polymeric micelles were of sustained release, where GB-SP/PVP2-1 extended the drug release for 48 hours. The MTT assay showed that all GB-SP/PVP dressings have good cytocompatibility, and in consequence, they can be used in further investigations on biomedical applications. In vivo tests on a rat model of a full-thickness wound showed rapid closure, indicating the success of the wound dressings in decreasing inflammation and promoting wound healing without scar formation. Therefore, topical administration of GB-SP/PVP1-0 and GB-SP/PVP2-1 wound dressings has a high potential for the treatment of diabetic wounds in inflammatory and proliferative phases of healing with high bioavailability and fewer systemic adverse effects.
Background and Objective: Glibenclamide (GB) is showing promising results in central nervous system (CNS) injuries treatment where intravenous administration of GB could overcome the oral limitations and assure maximum bioavailability. Dry powder of GB nanoparticles reconstituted for parenteral administration was prepared through electrospraying. Methods: The drug was incorporated with two polymers, polyvinylpyrrolidone (PVP) and Soluplus® (SP), at ratios 1:4 and 1:2 (GB/polymer). Different solvent mixtures were used to formulate the particles. Physicochemical characteristics were investigated. Results: The size of the GB-PVP nanoparticle ranged between (409-775) nm with a spherical, disk, fractured and, agglomerated morphology, while those of the GB-SP nanomicelles were of (447-785) nm with mostly irregular morphology, in consequence to the used solvents mixtures. The high encapsulation efficiency ≥ 98% reflects the well dispersed drug molecules within the polymer matrix, further confirmed by X-ray diffraction and infrared spectroscopy. GB-SP colloidal dispersions showed neutral zeta potentials with a cloud point of 36 ˚C, indicating prolonged circulation time and stability after parenteral administration. GB/SP nanomicelles at ratio 1:4 showed a sustained drug release reaching ≥ 94% in 36 hours. Conclusion: The GB-SP nanomicelles with extended drug release and regarding physicochemical properties represent a remarkable drug delivery system for parenteral administration.
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