In vitro characterization of alginate-chitosan hydrogels prepared with pH modification

Birnur Cömez; Sevinç Şahbaz; Suna Özbaş

In vitro characterization of alginate-chitosan hydrogels prepared with pH modification

Abstract

Hydrogels are biomaterials frequently used as carrier systems for wound care, tissue engineering, and local drug applications. Our study aimed to prepare and characterize hydrogels using chitosan and sodium alginate through pH modification. Mechanical properties (hardness, adhesiveness, cohesiveness, compressibility, and elasticity), viscosity, surface morphology, and cytotoxicity of polyion complex hydrogels containing different ratios of sodium alginate and chitosan were investigated. Mechanical properties were determined with a texture analyzer. The viscosity values of hydrogels varied between 12235 and 40743.3 cP. Hydrogel samples absorbed water up to 1000 – 1400% of their weight. The effect of pH and polymer concentration on the structural and mechanical properties of alginate-chitosan hydrogels was demonstrated. The findings showed that the decrease in pH improved the mechanical properties of alginate-chitosan hydrogels and increased the viscosity. The concentrations of chitosan and sodium alginate also altered the properties of hydrogels depending on pH. The formulation H5, which had the highest polymer ratio (3%) and lower pH, showed the highest hardness (0.285 ± 0.018 N), adhesiveness (0.824 ± 0.042 N. s), and compressibility (1.334±0.020 N.mm) values. The results showed that the prepared alginate-chitosan hydrogels are not cytotoxic (cell viability of over 80% in L-929 cell line) and safe for use in living organisms.

Keywords

References

[1] Khong TT, Aarstad OA, Skjåk-Bræk G, Draget KI, Vårum KM. Gelling concept combining chitosan and alginate—proof of principle. Biomacromolecules. 2013; 14(8): 2765-2771. https://doi.org/10.1021/bm400610b
[2] Ho TC, Chang CC, Chan HP, Chung TW, Shu CW, Chuang KP, Duh TH, Yang MH, Tyan YC. Hydrogels: properties and applications in biomedicine. Molecules. 2022; 27(9): 2902. https://doi.org/10.3390/molecules27092902
[3] Amasya G, Inal O, Sengel-Turk CT. SLN enriched hydrogels for dermal application: full factorial design study to estimate the relationship between composition and mechanical properties. Chem Phys Lipids. 2020; 228: 104889. https://doi.org/10.1016/j.chemphyslip.2020.104889
[4] Liu J, Jiang W, Xu Q, Zheng Y. Progress in antibacterial hydrogel dressing. Gels. 2022; 8(8): 503. https://doi.org/10.3390/gels8080503
[5] Cheaburu-Yilmaz CN, Yilmaz O, Kose FA, Bibire N. Chitosan-Graft-Poly(N-Isopropylacrylamide)/PVA cryogels as carriers for mucosal delivery of voriconazole. Polymers. 2019; 11(9): 1432. https://doi.org/10.3390/polym11091432
[6] Stoica AE, Chircov C, Grumezescu AM. Hydrogel dressings for the treatment of burn wounds: an up-to-date overview. Materials. 2020; 13(12): 2853. https://doi.org/10.3390/ma13122853
[7] Irimia T, Dinu-Pîrvu CE, Ghica MV, Lupuleasa D, Muntean DL, Udeanu DI, Popa L. Chitosan-based in situ gels for ocular delivery of therapeutics: a state-of-the-art review. Mar Drugs. 2018; 16(10): 373. https://doi.org/10.3390/md16100373
[8] Baysal K, Aroguz AZ, Adiguzel Z, Baysal BM. Chitosan/alginate crosslinked hydrogels: preparation, characterization and application for cell growth purposes. Int J Biol Macromol. 2013; 59: 342-348. https://doi.org/10.1016/j.ijbiomac.2013.04.073

[9] Wu Y, Rashidpour A, Almajano MP, Metón I. Chitosan-Based Drug Delivery System: Applications in Fish Biotechnology. Polymers. 2020; 12(5): 1177. https://doi.org/10.3390/polym12051177
[10] Wu T, Huang J, Jiang Y, Hu Y, Ye X, Liu D, Chen J. Formation of hydrogels based on chitosan/alginate for the delivery of lysozyme and their antibacterial activity. Food Chem. 2018; 240: 361-369. https://doi.org/10.1016/j.foodchem.2017.07.052
[11] Zhang M, Qiao X, Han W, Jiang T, Liu F, Zhao X. Alginate-chitosan oligosaccharide-ZnO composite hydrogel for accelerating wound healing. Carbohydr Polym. 2021; 266: 118100. https://doi.org/10.1016/j.carbpol.2021.118100
[12] Phan VHG, Mathiyalagan R, Nguyen MT, Tran TT, Murugesan M, Ho TN, Huong H, Yang DC, Li Y, Thambi T. Ionically cross-linked alginate-chitosan core-shell hydrogel beads for oral delivery of insulin. Int J Biol Macromol. 2022; 222: 262-271. https://doi.org/10.1016/j.ijbiomac.2022.09.165
[13] Abka-khajouei R, Tounsi L, Shahabi N, Patel AK, Abdelkafi S, Michaud P. Structures, properties and applications of alginates. Mar Drugs. 2022; 20(6): 364. https://doi.org/10.3390/md20060364
[14] Liu Q, Li Q, Xu S, Zheng Q, Cao X. Preparation and properties of 3D printed alginate–chitosan polyion complex hydrogels for tissue engineering. Polymers. 2018; 10(6): 664. https://doi.org/10.3390/polym10060664
[15] Rassu G, Salis A, Porcu EP, Giunchedi P, Roldo M, Gavini E. Composite chitosan/alginate hydrogel for controlled release of deferoxamine: a system to potentially treat iron dysregulation diseases. Carbohydr Polym. 2016; 136: 1338-1347. https://doi.org/10.1016/j.carbpol.2015.10.048
[16] Luo F, Sun TL, Nakajima T, Kurokawa T, Zhao Y, Sato K, Ihsan AB, Li X, Guo H, Gong JP. Oppositely charged polyelectrolytes form tough, self-healing, and rebuildable hydrogels. Adv Mater. 2015; 27(17): 2722-2727. https://doi.org/10.1002/adma.201500140
[17] Ahmadi F, Oveisi Z, Samani SM, Amoozgar Z. Chitosan based hydrogels: characteristics and pharmaceutical applications. Res Pharm Sci. 2015; 10(1): 1-16.
[18] Özcan Bülbül E, Siafaka PI, Mutlu G, Üstündağ Okur N. Preliminary study for the development of potent hydrogels for local drug delivery applications. J Pharm Technol. 2021; 2(1): 65-71. https://doi.org/10.37662/jpt.2021.9
[19] Stepanovska J, Otahal M, Hanzalek K, Supova M, Matejka R. pH modification of high-concentrated collagen bioinks as a factor affecting cell viability, mechanical properties, and printability. Gels. 2021; 7(4): 252. https://doi.org/10.3390/gels7040252
[20] Salazar-Brann SA, Patiño-Herrera R, Navarrete-Damián J, Louvier-Hernández JF. Electrospinning of chitosan from different acid solutions. AIMS Bioeng. 2021; 8(1): 112-129. https://doi.org/10.3934/bioeng.2021011
[21] Patel P, Patel P. Formulation and evaluation of clindamycin HCl in situ gel for vaginal application. Int J Pharm Investig. 2015; 5(1): 50-56. https://doi.org/10.4103/2230-973x.147233
[22] Rençber S, Cheaburu-Yilmaz CN, Köse FA, Yaprak Karavana S, Yilmaz O. Preparation and characterization of alginate and chitosan ipc based gel formulation for mucosal application. Cellul Chem Technol 2019; 53(7-8): 655-665. https://doi.org/10.35812/CelluloseChemTechnol.2019.53.64
[23] Şenyiğit ZA, Karavana SY, Eraç B, Gürsel Ö, Limoncu MH, Baloğlu E. Evaluation of chitosan based vaginal bioadhesive gel formulations for antifungal drugs. Acta Pharm. 2014; 64(2): 139-156. https://doi.org/10.2478/acph-2014-0013
[24] Sezer AD, Cevher E, Hatipoğlu F, Oğurtan Z, Baş AL, Akbuğa J. Preparation of fucoidan-chitosan hydrogel and its application as burn healing accelerator on rabbits. Biol Pharm Bull. 2008; 31(12): 2326-2333. https://doi.org/10.1248/bpb.31.2326
[25] Afzal S, Maswal M, Dar AA. Rheological behavior of pH responsive composite hydrogels of chitosan and alginate: Characterization and its use in encapsulation of citral. Colloids Surf B Biointerfaces. 2018; 169: 99-106. https://doi.org/10.1016/j.colsurfb.2018.05.002
[26] Hurler J, Engesland A, Poorahmary Kermany B, Škalko-Basnet N. Improved texture analysis for hydrogel characterization: gel cohesiveness, adhesiveness, and hardness. J Appl Polym Sci 2012; 125(1): 180-188. https://doi.org/10.1002/app.35414.
[27] Tan YTF, Peh KK, Al-Hanbali O. Effect of carbopol and polyvinylpyrrolidone on the mechanical, rheological, and release properties of bioadhesive polyethylene glycol gels. AAPS PharmSciTech. 2000; 1(3): 69-78. https://doi.org/10.1208/pt010324
[28] Cevher E, Sensoy D, Taha MAM, Araman A. Effect of thiolated polymers to textural and mucoadhesive properties of vaginal gel formulations prepared with polycarbophil and chitosan. AAPS PharmSciTech. 2008; 9(3): 953-965. https://doi.org/10.1208/s12249-008-9132-y
[29] Bektaş A, Cevher E, Güngör S, Özsoy Y. Design and evaluation of polysaccharide-based transdermal films for the controlled delivery of nifedipine. Chem Pharm Bull. 2014; 62(2): 144-152. https://doi.org/10.1248/cpb.c13-00579
[30] Patlolla VGR, Holbrook WP, Gizurarson S, Kristmundsdottir P. Evaluation of in vitro mucoadhesiveness and texture profile analysis of doxycycline in situ hydrogels. Pharmazie. 2020; 75(1): 7-12. https://doi.org/10.1691/ph.2020.9122
[31] Cevher E, Taha MAM, Orlu M, Araman A. Evaluation of mechanical and mucoadhesive properties of clomiphene citrate gel formulations containing carbomers and their thiolated derivatives. Drug Deliv. 2008; 15(1): 57-67. https://doi.org/10.1080/10717540701829234
[32] Şenyiğit T, Tekmen I, Sönmez Ü, Santi P, Özer Ö. Deoxycholate hydrogels of betamethasone-17-valerate intended for topical use: in vitro and in vivo evaluation. Int J Pharm. 2011; 403(1-2): 123-129. https://doi.org/10.1016/j.ijpharm.2010.10.036
[33] Kim SJ, Park SJ, Kim SI. Swelling behavior of interpenetrating polymer network hydrogels composed of poly (vinyl alcohol) and chitosan. React Funct Polym. 2003; 55(1): 53-59. https://doi.org/10.1016/s1381-5148(02)00214-6
[34] Wang G, Wang X, Huang L. Feasibility of chitosan-alginate (chi-alg) hydrogel used as scaffold for neural tissue engineering: a pilot study in vitro. Biotechnol Biotechnol Equip. 2017; 31(4):766-773. https://doi.org/10.1080/13102818.2017.1332493
[35] Yang S, Leong KF, Du Z, Chua CK. The design of scaffolds for use in tissue engineering. Part I. Traditional factors. Tissue Eng. 2001; 7(6): 679-689. https://doi.org/10.1089/107632701753337645
[36] Cannella V, Altomare R, Chiaramonte G, Di Bella S, Mira F, Russotto L, Pisano P, Guercio A. Cytotoxicity evaluation of endodontic pins on L929 cell line. BioMed Res Int. 2019; 2019: 1-5. https://doi.org/10.1155/2019/3469525
[37] Salehi M, Bagher Z, Kamrava SK, Ehterami A, Alizadeh R, Farhadi M, Falah M, Komeili A. Alginate/chitosan hydrogel containing olfactory ectomesenchymal stem cells for sciatic nerve tissue engineering. J Cell Physiol. 2019; 234(9): 15357-15368. https://doi.org/10.1002/jcp.28183

Details

Primary Language

English

Subjects

Pharmacology and Pharmaceutical Sciences (Other)

Journal Section

Research Article

Authors

Birnur Cömez ^* This is me
0000-0002-9961-5560
Türkiye

Sevinç Şahbaz
0000-0001-9195-5563
Türkiye

Suna Özbaş
0000-0002-1721-7543
Türkiye

Publication Date

June 28, 2025

Submission Date

May 28, 2023

Acceptance Date

August 16, 2023

Published in Issue

Year 2023 Volume: 27 Number: 6

IZ

https://izlik.org/JA43WX68PR

Cite

RIS / Bibtex

APA

Cömez, B., Şahbaz, S., & Özbaş, S. (2025). In vitro characterization of alginate-chitosan hydrogels prepared with pH modification. Journal of Research in Pharmacy, 27(6), 2405-2415. https://izlik.org/JA43WX68PR

AMA

1.Cömez B, Şahbaz S, Özbaş S. In vitro characterization of alginate-chitosan hydrogels prepared with pH modification. J. Res. Pharm. 2025;27(6):2405-2415. https://izlik.org/JA43WX68PR

Chicago

Cömez, Birnur, Sevinç Şahbaz, and Suna Özbaş. 2025. “In Vitro Characterization of Alginate-Chitosan Hydrogels Prepared With PH Modification”. Journal of Research in Pharmacy 27 (6): 2405-15. https://izlik.org/JA43WX68PR.

EndNote

Cömez B, Şahbaz S, Özbaş S (July 1, 2025) In vitro characterization of alginate-chitosan hydrogels prepared with pH modification. Journal of Research in Pharmacy 27 6 2405–2415.

IEEE

[1]B. Cömez, S. Şahbaz, and S. Özbaş, “In vitro characterization of alginate-chitosan hydrogels prepared with pH modification”, J. Res. Pharm., vol. 27, no. 6, pp. 2405–2415, July 2025, [Online]. Available: https://izlik.org/JA43WX68PR

ISNAD

Cömez, Birnur - Şahbaz, Sevinç - Özbaş, Suna. “In Vitro Characterization of Alginate-Chitosan Hydrogels Prepared With PH Modification”. Journal of Research in Pharmacy 27/6 (July 1, 2025): 2405-2415. https://izlik.org/JA43WX68PR.

JAMA

1.Cömez B, Şahbaz S, Özbaş S. In vitro characterization of alginate-chitosan hydrogels prepared with pH modification. J. Res. Pharm. 2025;27:2405–2415.

MLA

Cömez, Birnur, et al. “In Vitro Characterization of Alginate-Chitosan Hydrogels Prepared With PH Modification”. Journal of Research in Pharmacy, vol. 27, no. 6, July 2025, pp. 2405-1, https://izlik.org/JA43WX68PR.

Vancouver

1.Birnur Cömez, Sevinç Şahbaz, Suna Özbaş. In vitro characterization of alginate-chitosan hydrogels prepared with pH modification. J. Res. Pharm. [Internet]. 2025 Jul. 1;27(6):2405-1. Available from: https://izlik.org/JA43WX68PR