Diabetic Foot Ulcers Healing Promoted by Novel Glibenclamide-loaded Micelle Wound Dressing

Maryam Al-Ghezi *

Department of Chemical Engineering, College of Engineering, University of Baghdad, Jadiriya-10071, Baghdad, Iraq.

Raghad F. Almilly

Department of Chemical Engineering, College of Engineering, University of Baghdad, Jadiriya-10071, Baghdad, Iraq.

Wedad K. Ali

Department of Pharmaceutics, College of Pharmacy, Al-Mustansiriyah University, Qadisiya st.-10015, Baghdad, Iraq.

*Author to whom correspondence should be addressed.


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.

Keywords: Diabetic wound dressing, hybrid micelles, soluplus, glibenclamide, electrospraying

How to Cite

Al-Ghezi, M., Almilly, R. F. and Ali, W. K. (2022) “Diabetic Foot Ulcers Healing Promoted by Novel Glibenclamide-loaded Micelle Wound Dressing”, Journal of Pharmaceutical Research International, 34(53B), pp. 36–49. doi: 10.9734/jpri/2022/v34i53B7230.


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Zhou P, Zhou H, Shu J, Fu S, Yang Z. Skin wound healing promoted by novel curcumin-loaded micelle hydrogel, Ann. Transl. Med. 2021;9(14):1152–1152.

DOİ: 10.21037/atm-21-2872

Saghazadeh S et al. Drug delivery systems and materials for wound healing applications, Adv. Drug Deliv. Rev. 2018;127:138–166.

DOİ: 10.1016/j.addr.2018.04.008

Association AD. Diagnosis and Classification of Diabetes Mellitus, Diabetes Care2014;37(Supplement 1): S81–S90.

DOİ: 10.2337/DC14-S081

WHO Global Report on Diabetes, Global Report on Diabetes; 2016.

Accessed: Nov. 19, 2021. [Online].

Available: https://www.who.int/publications/i/item/9789241565257.

Patel S, Srivastava S, Singh MR, Singh D. Mechanistic insight into diabetic wounds: Pathogenesis, molecular targets and treatment strategies to pace wound healing, Biomed. Pharmacother. 2018;112:108615, 2019.

DOİ: 10.1016/j.biopha.2019.108615

Siddiqui AR, Bernstein JM. Chronic wound infection: Facts and controversies, Clin. Dermatol. 2010;28(5): 519–526.

DOİ: 10.1016/J.CLINDERMATOL.2010.03.009

Gianino E, Miller C, Gilmore J. Smart wound dressings for diabetic chronic wounds, Bioengineering. 2018;5:3.

DOİ: 10.3390/bioengineering5030051

Zhang P, Lu J, Jing Y, Tang S, Zhu D, Bi Y. Global epidemiology of diabetic foot ulceration: a systematic review and meta-analysis†, Ann. Med. 2017;49(2):106–116.


Salazar JJ, Ennis WJ, Koh TJ. Diabetes medications: Impact on inflammation and wound healing, J. Diabetes Complications. 2016;30(4):746–752.

DOİ: 10.1016/j.jdiacomp.2015.12.017

Mirza RE, Fang MM, Weinheimer-Haus EM, Ennis WJ, Koh TJ. Sustained inflammasome activity in macrophages impairs wound healing in type 2 diabetic humans and mice, Diabetes. 2014;63(3):1103–1114.

DOİ: 10.2337/db13-0927

Lamkanfi M et al. Glyburide inhibits the Cryopyrin/Nalp3 inflammasome, J. Cell Biol. 2009;187(1):61–70.

DOİ: 10.1083/jcb.200903124

Bodiga VL et al. In vitro biological evaluation of glyburide as potential inhibitor of collagenases, Int. J. Biol. Macromol.. 2014;70: 187–192.

DOİ: 10.1016/j.ijbiomac.2014.06.054

Lin YW, Liu PS, Pook KA, Wei LN. Glyburide and retinoic acid synergize to promote wound healing by anti-inflammation and RIP140 degradation. Sci. Rep. 2018;8(1):1–8.

DOİ: 10.1038/s41598-017-18785-x

Cam ME et al. Accelerated diabetic wound healing by topical application of combination oral antidiabetic agents-loaded nanofibrous scaffolds: An in vitro and in vivo evaluation study,” Mater. Sci. Eng. C. 2021;119:111586.

DOİ: 10.1016/j.msec.2020.111586

Madhukiran DR, Jha A, Kumar M, Ajmal G, Bonde GV, Mishra B. Electrospun nanofiber-based drug delivery platform: advances in diabetic foot ulcer management. Expert Opin. Drug Deliv. 2021;18(1):25–42.

DOİ: 10.1080/17425247.2021.1823966

Zhu C et al. Supersaturated polymeric micelles for oral silybin delivery: the role of the Soluplus–PVPVA complex, Acta Pharm. Sin. B. 2019;9(1):107–117.

DOİ: 10.1016/j.apsb.2018.09.004

Salah I, Shamat MA, Cook MT. Soluplus solutions as thermothickening materials for topical drug delivery, J. Appl. Polym. Sci. 2019;136(1):1–9.

DOİ: 10.1002/app.46915

Paaver U et al. Soluplus graft copolymer: Potential novel carrier polymer in electrospinning of nanofibrous drug delivery systems for wound therapy, Biomed Res. Int. 2014:14–18.

DOİ: 10.1155/2014/789765

Nasr M, Karandikar H, Abdel-Aziz RTA, Moftah N, Paradkar A. Novel nicotinamide skin-adhesive hot melt extrudates for treatment of acne, Expert Opin. Drug Deliv. 2018;15(12):1165–1173.

DOİ: 10.1080/17425247.2018.1546287

Mosmann T, Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays, J. Immunol. Methods. 1983;65(1–2):55–63.

DOİ: 10.1016/0022-1759(83)90303-4

Grela E, Kozłowska J, Grabowiecka A. Current methodology of MTT assay in bacteria – A review, Acta Histochem. 2018;120(4):303–311.

DOİ: 10.1016/j.acthis.2018.03.007

Schindl A, Schindl M, Pernerstorfer-Schön H, Kerschan K, Knobler R, Schindl L. Diabetic neuropathic foot ulcer: Successful treatment by low-intensity laser therapy, Dermatology. 1999;198(3):314–316.

DOİ: 10.1159/000018140

Tim CR et al. Mitochondrial dynamics (fission and fusion) and collagen production in a rat model of diabetic wound healing treated by photobiomodulation: comparison of 904 nm laser and 850 nm light-emitting diode (LED), J. Photochem. Photobiol. B Biol. 2019;41–47.


Levengood SL, Erickson AE, Chien Chang F, Zhang M. Chitosan-poly(caprolactone) nanofibers for skin repair, J. Mater. Chem. vol. 2017;5(9):1822–1833.

DOİ: 10.1039/C6TB03223K

Takla PG. Glibenclamide, in Analytical Profiles of Drug Substances. 1981;10: 337–355.

Wang Y et al. The role of particle size of glyburide crystals in improving its oral absorption, Drug Deliv. Transl. Res. 2017;7(3):428–438.

DOİ: 10.1007/s13346-017-0378-3

Liu P et al. Soluplus-mediated diosgenin amorphous solid dispersion with high solubility and high stability: Development, characterization and oral bioavailability, Drug Des. Devel. Ther. 2020;14:2959–2975.

DOİ: 10.2147/DDDT.S253405

Homayouni A, Sadeghi F, Nokhodchi A, Varshosaz J, Garekani HA. Preparation and characterization of celecoxib dispersions in soluplus®: Comparison of spray drying and conventional methods, Iran. J. Pharm. Res.. 2015;14(1):35–50.

DOİ: 10.22037/ijpr.2015.1621

Cui L, Liu ZP, Yu DG, Zhang SP, Bligh SWA, Zhao N. Electrosprayed core-shell nanoparticles of PVP and shellac for furnishing biphasic controlled release of ferulic acid. Colloid Polym. Sci. 2014;292(9):2089–2096,

DOİ: 10.1007/s00396-014-3226-8

Kim GM, Le KHT, Giannitelli SM, Lee YJ, Rainer A, Trombetta M. Electrospinning of PCL/PVP blends for tissue engineering scaffolds, J. Mater. Sci. Mater. Med. 2013;246(24)(6):1425–1442.

DOİ: 10.1007/S10856-013-4893-6

Wang JC, Zheng H, Chang MW, Ahmad Z, Li JS. Preparation of active 3D film patches via aligned fiber electrohydrodynamic (EHD) printing, Sci. Rep. 2017;7.

DOİ: 10.1038/SREP43924

Punčochová K et al. The Combined Use of Imaging Approaches to Assess Drug Release from Multicomponent Solid Dispersions, Pharm. Res. 2017;34(5):990–1001.

DOİ: 10.1007/s11095-016-2018-x

Lee CH et al. Enhancement of diabetic wound repair using biodegradable nanofibrous metformin-eluting membranes: In vitro and in vivo, ACS Appl. Mater. Interfaces. 2014;6(6):3979–3986.

DOİ: 10.1021/am405329g

Merrell JG, McLaughlin SW, Tie L, Laurencin CT, Chen AF, Nair LS. Curcumin-loaded poly(ε-caprolactone) nanofibres: Diabetic wound dressing with anti-oxidant and anti-inflammatory properties, Clin. Exp. Pharmacol. Physiol. 2009;36(12):1149–1156.

DOİ: 10.1111/J.1440-1681.2009.05216.X