Evaluation of Diabetic Wound Healing Activity of Novel Quercetin Topical Preparations

Christofori Maria Ratna Rini Nastiti, Ellisia Michelina, Fabiola Rani Wijayanti, Michael Raharja Gani

Abstract


Diabetic wound needs effective pharmacotherapy in order to accelerate the wound healing process and to prevent further infection. Quercetin (QUE) is one of flavonols which ispotential as an active ingredient for diabetic wound therapy, due to its anti-inflammatory and antioxidant activities.  This current study evidenced wound healing activity of QUE topical preparations on the open wound of diabetic-induced subjects preclinically. The investigation focused on topical administration of QUE nanoemulgels and QUE micellar gels (0.2% w/w of QUE) on groups of diabetic-induced male Wistar rats. The quality of preparations in terms of organoleptic performance, pH, viscosity and spread-ability was physically characterized prior to topical administration to the wound. Punch biopsy (5mm) was applied to create the open wound. The visual observation of wound contraction area (in mm2) was carried out every three days. On the day 12th, after sacrificing the subjects, the wounded tissues were removed, fixed in 10% formalin and prepared for histology examination-hematoxylin and eosin staining. The results showed that the QUE nanoemulgels and QUE micellar gels were relatively comparable onthe physical quality as well as the wound healing activity. Their wound healing activities were remarkably faster compared to the untreated control group and it was showed fromthe histology study that the QUE nanoemulgels and QUE micellar gels successfully accelerate the wound healing process to the proliferation step if it was compared the untreated. In conclusion, QUE nanoemulgels and QUE micellar gels were potential to develop to accelerate the diabetic wound healing process.    

Keywords


Biopsy; Diabetic; Micellar; Quercetin; Wound

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References


Ahmed, O.M., Mohamed, T., Moustafa, H., Hamdy, H., Ahmed, R.R., Aboud, E., 2018. Quercetin and low level laser therapy promote wound healing process in diabetic rats via structural reorganization and modulatory effects on inflammation and oxidative stress. Biomed. Pharmacother., 101:58–73.

Alberti, T.S., Coelho, D., Voytena, A, Pitz, H., de Pra, M., Mazzarino, L., et al., 2017. Nanotechnology: A promising tool towards wound healing. Curr. Pharm. Des., 23(24):3515–28.

Azeem, M., Hanif, M., Mahmood, K., Ameer, N., Chughtai, F.R.S., Abid, U., 2023. An insight into anticancer, antioxidant, antimicrobial, antidiabetic and anti-inflammatory effects of quercetin: A review. Polym. Bull., 80(1):241–62.

Bahloul, B., Bnina, E., Ben, Hamdi, A., Castillo, L., Baccar, D., Kalboussi, N., et al., 2023. Development of a Low-Temperature Process for the Formulation of Nanoemulsion-Gel Encapsulating Essential Oil: Investigation on the Wound Healing Effect. Preprints, 2023080150.

Barroso, A., Mestre, H., Ascenso, A., Simões, S., Reis, C., 2020. Nanomaterials in wound healing: From material sciences to wound healing applications. Nano Sel., 1(5):443–60.

Bashir, M., Ahmad, J., Asif, M., Irfan, M., Ibrahim, A.Y., Asghar, S., et al., 2021. Nanoemulgel, an innovative carrier for diflunisal topical delivery with profound anti-inflammatory effect: In vitro and in vivo evaluation. Int. J. Nanomedicine., 16:1457-72.

Beken, B., Serttas, R., Yazicioglu, M., Turkekul, K., Erdogan, S., 2020. Quercetin Improves Inflammation, Oxidative Stress, and Impaired Wound Healing in Atopic Dermatitis Model of Human Keratinocytes. Pediatr. Allergy. Immunol. Pulmonol., 33(2):69–79.

Burgess, J.L., Wyant, W.A., Abujamra, B.A., Kirsner, R.S., Jozic, I., 2021. Diabetic Wound-Healing Science. Medicina (Kaunas)., 57(10):1072.

Chang, M., 2016. Restructuring of the extracellular matrix in diabetic wounds and healing: A perspective. Pharmacol. Res.,107:243–8.

Chen, J., Qin, S., Liu, S., Zhong K, Jing Y, Wu X, et al., 2023. Targeting matrix metalloproteases in diabetic wound healing. Front. Immunol., 14:1089001.

Darabian, B., Bagheri, H., Mohammadi, S., 2020. Improvement in mechanical properties and biodegradability of PLA using poly (ethylene glycol) and triacetin for antibacterial wound dressing applications. Prog. Biomater., 9:45–64.

Deng, L., Du, C., Song, P., Chen, T., Rui, S., Armstrong, D.G., et al. 2021. The role of oxidative stress and antioxidants in diabetic wound healing. Oxid. Med. Cell. Longev., 2021.

Falanga, V., 2005. Wound healing and its impairment in the diabetic foot. Lancet., 366(9498):1736–43.

Fiume, M.Z., 2003. Final report on the safety assessment of triacetin. Int. J. Toxicol., 22(Suppl.2):1–10.

Ghareeb, MM., 2019. Design and in vitro characterization of a topical nanoemulsion-enriched hydrogel of econazole nitrate. J. Appl. Pharm. Sci., 9(1):51–7.

Garg, A., Aggarwal, D., Garg, S.K., Singla, A., 2002. Spreading of Semisolid Formulations: An Update. Pharm. Technol. 26(9):84–105.

Ghobadi, A., Ahmadi, S.P., Jalilian, M., Abdi, A., Manouchehri, S., 2020. Evaluation of factors affecting the severity of diabetic foot ulcer in patients with diabetes referred to a diabetes centre in Kermanshah. Diabetes, Metab. Syndr. Obes., 2020:693–703.

Greenhalgh, D.G., 2003. Wound healing and diabetes mellitus. Clin. Plast. Surg., 30(1):37–45.

Hazrati, M., Mehrabani, D., Japoni, A., Montasery, H., Azarpira, N., Hamidian-Shirazi, A.R., et al., 2010. Effect of honey on healing of Pseudomonas aeruginosa infected burn wounds in rat. J. Appl. Anim. Res., 37(2):161–5.

Hou, D.D., Zhang, W., Gao, Y.L., Sun, Y., Wang, H.X., Qi, R.Q., et al., 2019. Anti-inflammatory effects of quercetin in a mouse model of MC903-induced atopic dermatitis. Int. Immunopharmacol., 74:105676.

Ilić, T., Pantelić, I., Savić, S., 2021. The implications of regulatory framework for topical semisolid drug products: From critical quality and performance attributes towards establishing bioequivalence. Pharmaceutics., 13(5):710.

Jadhav, R.P., Koli, V.W., Kamble, A.B., Bhutkar, M.A., 2020. A Review on Nanoemulsion. Asian J. Res. Pharm. Sci., 10(2):103–8.

Jangde, R., Srivastava, S., Singh, M.R., Singh, D., 2018. In vitro and In vivo characterization of quercetin loaded multiphase hydrogel for wound healing application. Int. J. Biol. Macromol., 115:1211–7.

Jalilian, M., Ahmadi, S.P., Oubari, S., 2020. Factors related to severity of diabetic foot ulcer: a systematic review. Diabetes, Metab. Syndr. Obes., 13:1835–42.

Kant, V., Jangir, B.L., Sharma, M., Kumar, V., Joshi, V.G., 2021. Topical application of quercetin improves wound repair and regeneration in diabetic rats. Immunopharmacol. Immunotoxicol., 243(5):536–53.

Lesjak, M., Beara, I., Simin, N., Pintać, D., Majkić, T., Bekvalac, K., et al. 2018. Antioxidant and anti-inflammatory activities of quercetin and its derivatives. J. Funct. Foods., 40:68–75.

Li, Y., Yao, J., Han, C., Yang, J., Chaudhry, M.T., Wang, S., et al., 2016. Quercetin, inflammation and immunity. Nutrients., 8(3):167.

McKittrick, L.S., McKittrick, J.B., Risley, T.S., 1949. Transmetatarsal amputation for infection or gangrene in patients with diabetes mellitus. Ann. Surg., 130(4):826.

Namjoshi, S., Dabbaghi, M., Roberts, M.S., Grice, J.E., Mohammed ,Y., 2020. Quality by design: Development of the quality target product profile (QTPP) for semisolid topical products. Pharmaceutics., 12(3):287.

Nastiti, C.M.R.R., Dwiastuti, R., Riswanto, F.D.O., 2023. Novel Quercetin Nanoemulgel Optimization: Gelling Agents Evaluation and the Application of Response Surface Methodology. Int. J. Appl. Pharm. 15(1):72–8.

Nastiti, C.M.R.R., Ponto, T., Abd, E., Grice, J.E., Benson, H.A.E., Roberts, M.S., 2017. Topical Nano and Microemulsions for Skin Delivery. Pharmaceutics., 9(4):1–25.

Nastiti, C.M.R.R., Ponto, T., Mohammed, Y., Roberts, M.S., Benson, H.A.E., 2020. Novel Nanocarriers for Targeted Topical Skin Delivery of the Antioxidant Resveratrol. Pharmaceutics., 12(2):1–15.

Phaugat, P., Nishal, S., Dutt, R., Khansili, A., 2022. A co-additive nanoemulgel formulation of tretinoin and curcumin: Formulation and optimization. J. Appl. Pharm. Sci., 12(9):58–66.

Taskan, M., Yuce, H., Karatas, O., Gevrek, F., 2019. Topical quercetin gel application improved wound healing in wistar rats. Ann. Med. Res., 26(10):2397.

Tayeb, H.H., Felimban, R., Almaghrabi, S., Hasaballah, N., 2021. Nanoemulsions: Formulation, characterization, biological fate, and potential role against COVID-19 and other viral outbreaks. Colloid Interface Sci. Commun., 45:100533.

Tuglo, L.S., Nyande, F.K., Agordoh, P.D., Nartey, E.B., Pan, Z., Logosu, L., et al., 2022. Knowledge and practice of diabetic foot care and the prevalence of diabetic foot ulcers among diabetic patients of selected hospitals in the Volta Region, Ghana. Int. Wound J., 19(3):601–14.

Sharma, R., Jain, H., Pratibha, Godugu, C., Chella, N., 2023. Formulation and optimization of aceclofenac loaded hyaluronic-oleic acid based micellar gel for the management of osteoarthritis. J. Drug Deliv. Sci. Technol., 84:104560.

Sorg, H., Tilkorn, D.J., Hager, S., Hauser, J., Mirastschijski, U., 2017. Skin Wound Healing: An Update on the Current Knowledge and Concepts. Eur. Surg. Res., 58(1-2):81–94.

Veronica, E.F. and Dwiastuti, R., 2022. Formulation and evaluation of wound healing gel of white lead tree (Leucaena Leucocephala (lam.) de wit.) leaves extract. Int. J. App. Pharm., 14(1):275-280.

Xu, Z., Han, S., Gu, Z., Wu, J., 2020. Advances and impact of antioxidant hydrogel in chronic wound healing. Adv. Healthc. Mater., 9(5):1901502.

Yan, L., Vaghari-Tabari, M., Malakoti, F., Moein, S., Qujeq, D., Yousefi, B., et al., 2022. Quercetin: An effective polyphenol in alleviating diabetes and diabetic complications. Crit. Rev. Food Sci. Nutr., 1–24.




DOI: https://doi.org/10.24071/jpsc.007288

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