PREPARATION, CHARACTERIZATION AND EVALUATION OF GELLAN GUM/GLYCOL CHITOSAN BASED BAICALEIN HYDROGEL FOR WOUND HEALING

KIRAN D. BAVISKAR; SANTRAM LODHI

doi:10.22159/ijap.2024v16i2.49661

Authors

KIRAN D. BAVISKAR Sri Sathya Sai Institute of Pharmaceutical Sciences, Ram Krishna Dharmarth Foundation University, Gandhi Nagar, Bhopal-462033, Madhya Pradesh, India
SANTRAM LODHI Sri Sathya Sai Institute of Pharmaceutical Sciences, Ram Krishna Dharmarth Foundation University, Gandhi Nagar, Bhopal-462033, Madhya Pradesh, India https://orcid.org/0000-0002-7344-8573

DOI:

https://doi.org/10.22159/ijap.2024v16i2.49661

Keywords:

Baicalein, Hydrogel, Gellan gum, Glycol chitosan, Wound healing, Antioxidant

Abstract

Objective: The present work was emphasized on preparation, characterization and evaluation of baicalein loaded hydrogel to promote healing of wounds.

Methods: Baicalein loaded hydrogel was developed using Gellan gum and Glycol chitosan polymers. Prepared hydrogels were characterized for various parameters like Field Emission Scanning Electron Microscopy (FE-SEM), swelling property, entrapment efficiency, rheology and drug release. Wound healing study was investigated by using incision dead space wound models. Healing effect was assessed by measurement of tensile strength, collagen content, hydroxyproline content, protein content and antioxidant status.

Results: The percent entrapment efficiency of optimized hydrogel found to be 89.78±2.07 which resulted in controlled release of drug 85.03% in 12 h. The significant increased level of catalase and superoxide dismutase (SOD) was noticed in dead space wound model. The tensile strength study shows increase in collagen synthesis due to treatment with Baicalein loaded hydrogel. The higher collagen content, better granulation, increase in tensile strength was noticed. Histopathological examination also confirmed higher degree of re-epithelialization and enhanced cutaneous wound repair.

Conclusion: In conclusion, biodegradable Baicalein loaded hydrogel might have high potential for wound healing with improved oxidative status and extended release of Baicalein.

Downloads

Download data is not yet available.

References

Ahmed AS, Mandal UK, Taher M, Susanti D, Jaffri JM. PVA-PEG physically cross-linked hydrogel film as a wound dressing: experimental design and optimization. Pharm Dev Technol. 2018;23(8):751-60. doi: 10.1080/10837450.2017.1295067, PMID 28378604.

Bagher Z, Ehterami A, Safdel MH, Khastar H, Semiari H, Asefnejad A. Wound healing with alginate/chitosan hydrogel containing hesperidin in rat model. J Drug Deliv Sci Technol. 2020;55:101379. doi: 10.1016/j.jddst.2019.101379.

Muchova M, Munster L, Capakova Z, Mikulcova V, Kuritka I, Vicha J. Design of dialdehyde cellulose crosslinked poly(vinyl alcohol) hydrogels for transdermal drug delivery and wound dressings. Mater Sci Eng C Mater Biol Appl. 2020;116:111242. doi: 10.1016/j.msec.2020.111242, PMID 32806291.

Kaparekar PS, Poddar N, Anandasadagopan SK. Fabrication and characterization of chrysin-a plant polyphenol loaded alginate-chitosan composite for wound healing application. Colloids Surf B Biointerfaces. 2021;206:111922. doi: 10.1016/j.colsurfb.2021.111922, PMID 34157519.

Op ’t Veld RC, Walboomers XF, Jansen JA, Wagener FADTG. Design considerations for hydrogel wound dressings: strategic and molecular advances. Tissue Eng Part B Rev. 2020;26(3):230-48. doi: 10.1089/ten.TEB.2019.0281, PMID 31928151.

Liu G, Bao Z, Wu J. Injectable baicalin/F127 hydrogel with antioxidant activity for enhanced wound healing. Chin Chem Lett. 2020;31(7):1817-21. doi: 10.1016/j.cclet.2020.03.005.

Das S, Kumar V, Tiwari R, Singh L, Singh S. Recent advances in hydrogels for biomedical applications. Asian J Pharm Clin Res. 2018;11(11):62-8. doi: 10.22159/ajpcr.2018.v11i11.27921.

Lee S, Choi JH, Park A, Rim M, Youn J, Lee W. Advanced gellan gum-based glycol chitosan hydrogel for cartilage tissue engineering biomaterial. Int J Biol Macromol. 2020;158:452-60. doi: 10.1016/j.ijbiomac.2020.04.135, PMID 32335106.

Gohil SV, Padmanabhan A, Kan HM, Khanal M, Nair LS. Degradation-dependent protein release from enzyme-sensitive injectable glycol chitosan hydrogel. Tissue Eng Part A. 2021;27(13-14):867-80. doi: 10.1089/ten.TEA.2020.0124, PMID 32940146.

Zhang X, Pan Y, Li S, Xing L, Du S, Yuan G. Doubly crosslinked biodegradable hydrogels based on gellan gum and chitosan for drug delivery and wound dressing. Int J Biol Macromol. 2020;164:2204-14. doi: 10.1016/j.ijbiomac.2020.08.093, PMID 32798543.

Nair AB, Shah J, Aljaeid BM, Al-Dhubiab BE, Jacob S. Gellan gum-based hydrogel for the transdermal delivery of nebivolol: optimization and evaluation. Polymers (Basel). 2019;11(10):1699. doi: 10.3390/polym11101699, PMID 31623262.

Wei S, Xie J, Luo Y, Ma Y, Tang S, Yue P. Hyaluronic acid based nanocrystals hydrogels for enhanced topical delivery of drug: a case study. Carbohydr Polym. 2018;202:64-71. doi: 10.1016/j.carbpol.2018.08.112, PMID 30287044.

Barbosa AI, Torres TB, Lima SAC, Reis S. Hydrogels: a promising vehicle for the topical management of atopic dermatitis. Advanced Therapeutics. 2021;4(7):2100028. doi: 10.1002/adtp.202100028.

Haider M, Hassan MA, Ahmed IS, Shamma R. Thermogelling platform for baicalin delivery for versatile biomedical applications. Mol Pharm. 2018;15(8):3478-88. doi: 10.1021/acs.molpharmaceut.8b00480, PMID 29953815.

Zhou Q, Zhong L, Wei X, Dou W, Chou G, Wang Z. Baicalein and hydroxypropyl-γ-cyclodextrin complex in poloxamer thermal sensitive hydrogel for vaginal administration. Int J Pharm. 2013;454(1):125-34. doi: 10.1016/j.ijpharm.2013.07.006, PMID 23850236.

Kalaivanan P, Sivagnanam I, Rajamanickam M. Evaluation of wound healing activity of baicalein7-O-β-D-glucuronide isolated from leucas aspera. J Appl Pharm Sci. 2013;3(12):46-51. doi: 10.7324/JAPS.2013.31208.

Manconi M, Manca ML, Caddeo C, Cencetti C, di Meo C, Zoratto N. Preparation of gellan-cholesterol nanohydrogels embedding baicalin and evaluation of their wound healing activity. Eur J Pharm Biopharm. 2018;127:244-9. doi: 10.1016/j.ejpb.2018.02.015, PMID 29499300.

Mir Palomo S, Nacher A, Diez Sales O, Ofelia Vila Buso MA, Caddeo C, Manca ML. Inhibition of skin inflammation by baicalin ultradeformable vesicles. Int J Pharm. 2016;511(1):23-9. doi: 10.1016/j.ijpharm.2016.06.136, PMID 27374324.

Bashir S, Teo YY, Ramesh S, Ramesh K. Synthesis and characterization of karaya gum-g- poly (acrylic acid) hydrogels and in vitro release of hydrophobic quercetin. Polymer. 2018;147:108-20). doi: 10.1016/j.polymer.2018.05.071.

Pushpalatha R, Selvamuthukumar S, Kilimozhi D. Cyclodextrin nanosponge based hydrogel for the transdermal co-delivery of curcumin and resveratrol: development, optimization, in vitro and ex vivo evaluation. J Drug Deliv Sci Technol. 2019;52:55-64. doi: 10.1016/j.jddst.2019.04.025.

Qindeel M, Ahmed N, Sabir F, Khan S, Ur-Rehman A. Development of novel pH-sensitive nanoparticles loaded hydrogel for transdermal drug delivery. Drug Dev Ind Pharm. 2019;45(4):629-41. doi: 10.1080/03639045.2019.1569031, PMID 30633578.

Dey M, Ghosh B, Giri TK. Enhanced intestinal stability and pH-sensitive release of quercetin in GIT through gellan gum hydrogels. Colloids Surf B Biointerfaces. 2020;196:111341. doi: 10.1016/j.colsurfb.2020.111341, PMID 32916438.

Lodhi S, Jain AP, Rai G, Yadav AK. Preliminary investigation for wound healing and anti-inflammatory effects of Bambusa vulgaris leaves in rats. J Ayurveda Integr Med. 2016;7(1):14-22. doi: 10.1016/j.jaim.2015.07.001, PMID 27297505.

Kuwano H, Yano K, Ohno S, Ikebe M, Kitamura K, Toh Y. Dipyridamole inhibits early wound healing in rat skin incisions. J Surg Res. 1994;56(3):267-70. doi: 10.1006/jsre.1994.1042, PMID 8145544.

Shirwaikar A, Shenoy R, Udupa AL, Udupa SL, Shetty S. Wound healing property of ethanolic extract of leaves of Hyptis suaveolens with supportive role of antioxidant enzymes. Indian J Exp Biol. 2003;41(3):238-41, PMID 15267154.

Woessner JF. The determination of hydroxyproline in tissue and protein samples containing small proportions of this imino acid. Arch Biochem Biophys. 1961;93(2):440-7. doi: 10.1016/0003-9861(61)90291-0.

Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the folin phenol reagent. J Biol Chem. 1951;193(1):265-75. doi: 10.1016/S0021-9258(19)52451-6, PMID 14907713.

Beers RF, Sizer IW. A spectrophotometric method for measuring the breakdown of hydrogen peroxide by catalase. J Biol Chem. 1952;195(1):133-40. doi: 10.1016/S0021-9258(19)50881-X, PMID 14938361.

Misra HP, Fridovich I. The role of superoxide anion in the autoxidation of epinephrine and a simple assay for superoxide dismutase. J Biol Chem. 1972;247(10):3170-5. doi: 10.1016/S0021-9258(19)45228-9, PMID 4623845.

Moron MS, Depierre JW, Mannervik B. Levels of glutathione, glutathione reductase and glutathione S-transferase activities in rat lung and liver. Biochim Biophys Acta. 1979;582(1):67-78. doi: 10.1016/0304-4165(79)90289-7, PMID 760819.

Mcmanus JF, Mowry RW. Staining methods histologic and histochemical. New York: Harper & Row; 1965.

Dahiya S, Rani R, Kumar S, Dhingra D, Dilbaghi N. Chitosan-gellan gum bipolymeric nanohydrogels-a potential nanocarrier for the delivery of epigallocatechin gallate. BioNanoSci. 2017;7(3):508-20. doi: 10.1007/s12668-017-0416-0.

El-Kased RF, Amer RI, Attia D, Elmazar MM. Honey-based hydrogel: in vitro and comparative in vivo evaluation for burn wound healing. Sci Rep. 2017;7(1):9692. doi: 10.1038/s41598-017-08771-8, PMID 28851905.

Gupta A, Kowalczuk M, Heaselgrave W, Britland ST, Martin C, Radecka I. The production and application of hydrogels for wound management: a review. Eur Polym J. 2019;111:134-51. doi: 10.1016/j.eurpolymj.2018.12.019.

Han N, Johnson J, Lannutti JJ, Winter JO. Hydrogel-electrospun fiber composite materials for hydrophilic protein release. J Control Release. 2012;158(1):165-70. doi: 10.1016/j.jconrel.2011.09.094, PMID 22001869.

Hoare TR, Kohane DS. Hydrogels in drug delivery: progress and challenges. Polymer. 2008;49(8):1993-2007. doi: 10.1016/j.polymer.2008.01.027.

Naghizadeh Z, Karkhaneh A, Khojasteh A. Self-crosslinking effect of chitosan and gelatin on alginate based hydrogels: injectable in situ forming scaffolds. Mater Sci Eng C Mater Biol Appl. 2018;89:256-64. doi: 10.1016/j.msec.2018.04.018, PMID 29752097.

Gupta RK, Kumar S, Trivedi A, Verma R, Yogesh. Vitamin C and its role in body. Int J Pharm Pharm Sci. 2022;14(2):1-5. doi: 10.22159/ijpps.2022v14i2.43394.

Li BQ, Fu T, Gong WH, Dunlop N, Kung H, Yan Y. The flavonoid baicalin exhibits anti-inflammatory activity by binding to chemokines. Immunopharmacology. 2000;49(3):295-306. doi: 10.1016/S0162-3109(00)00244-7.

Hu Z, Guan Y, Hu W, Xu Z, Ishfaq M. An overview of pharmacological activities of baicalin and its aglycone baicalein: new insights into molecular mechanisms and signaling pathways. Iran J Basic Med Sci. 2022;25(1):14-26. doi: 10.22038/IJBMS.2022.60380.13381, PMID 35656442.