Abstract
An oxidized levan–chitosan (OLC) cross-linked hydrogel, a 3D network polymeric material, was prepared. Spectroscopic techniques confirmed the oxidation of levan and imine bond formation during cross-linking mechanism. The gelation time for OLC was less than 10 min and the gel exhibited viscoelastic properties with highly interconnected porous structures. The obtained OLC-gel exhibited better thermal stability compared to pristine levan. It was found that the OLC exhibited pH-dependent swelling behavior. The swelling ratio of OLC-gel at three different pH values indicates high hydrophilic nature in the order of pH 2.6 > pH 9.0 > pH 7.4. The hemolytic activity (3%) shown by the hydrogel was found to be within the clinical acceptance level (< 5%). OLC-gel loaded with turmeric oleoresin with 8.28% curcumin content showed a sustained release rate over 24 h. The kinetic release profile of the OLC-gel followed the Korsmeyer–Peppas model with non-Fickian release transport. The synthesized OLC-gel exhibited good cytocompatibility when tested against L929 fibroblast cells. The formed OLC-gel supported cell adhesion and proliferation of fibroblast cells which could support tissue regeneration at the wound site. The characteristics of OLC-gels suggested that OLC has excellent potential to serve as a wound dressing material.
Graphical abstract
Similar content being viewed by others
Data availability
Authors declare that the data presented in this paper will be made available upon request.
References
Farahani M, Shafiee A (2021) Wound healing: from passive to smart dressings. Adv Healthc Mater 10:1–32
Naahidi S, Jafari M, Logan M, Wang Y, Yuan Y, Bae H, Dixon B, Chen P (2017) Biocompatibility of hydrogel-based scaffolds for tissue engineering applications. Biotechnol Adv 35:530–544
Sahiner N, Sagbas S, Sahiner M, Silan C, Aktas N, Turk M (2016) Biocompatible and biodegradable poly(tannic acid) hydrogel with antimicrobial and antioxidant properties. Int J Biol Macromol 82:150–159
Hama R, Ulziibayar A, Reinhardt JW, Watanabe T, Kelly J, Shinoka T (2023) Recent developments in biopolymer-based hydrogels for tissue engineering applications. Biomolecules 13:280
Yalçın D, Top A (2022) Novel biopolymer-based hydrogels obtained through crosslinking of keratose proteins using tetrakis(hydroxymethyl) phosphonium chloride. Iran Polym J 31:1057–1067
Del Prado-Audelo ML, Caballero-Florán IH, Mendoza-Muñoz N, Giraldo-Gomez D, Sharifi-Rad J, Patra JK, González-Torres M, Florán B, Cortes H, Leyva-Gómez G (2022) Current progress of self-healing polymers for medical applications in tissue engineering. Iran Polym J 31:7–29
Yang J, Wang S (2023) Polysaccharide-based multifunctional hydrogel bio-adhesives for wound healing: a review. Gels 138:1–24
Osman A, Lin E, Hwang DS (2023) A sticky carbohydrate meets a mussel adhesive: catechol-conjugated levan for hemostatic and wound healing applications. Carbohydr Polym 299:120172
Chidambaram JSCA, Veerapandian B, Sarwareddy KK, Mani KP, Shanmugam SR, Venkatachalam P (2019) Studies on solvent precipitation of levan synthesized using Bacillus subtilis MTCC 441. Heliyon 5:e02414
Combie J, Öner ET (2018) From healing wounds to resorbable electronics, levan can fill bioadhesive roles in scores of markets. Bioinspir Biomim 14:011001
Peng J, Xu W, Ni D, Zhang W, Zhang T, Guang C, Mu W (2019) Preparation of a novel water-soluble gel from Erwinia amylovora levan. Int J Biol Macromol 122:469–478
Hacıosmanoğlu GG, Doğruel T, Genç S, Oner ET, Can ZS (2019) Adsorptive removal of bisphenol A from aqueous solutions using phosphonated levan. J Hazard Mater 374:43–49
Bostan MS, Mutlu EC, Kazak H, Keskin SS, Oner ET, Eroglu MS (2014) Comprehensive characterization of chitosan/PEO/levan ternary blend films. Carbohydr Polym 102:993–1000
Sezer AD, Kazak H, Öner ET, Akbua J (2011) Levan-based nanocarrier system for peptide and protein drug delivery: optimization and influence of experimental parameters on the nanoparticle characteristics. Carbohydr Polym 84:358–363
Osman A, Oner ET, Eroglu MS (2017) Novel levan and pNIPA temperature sensitive hydrogels for 5-ASA controlled release. Carbohydr Polym 165:61–70
Davoudi Z, Peroutka-Bigus N, Bellaire B, Jergens A, Wannemuehler M, Wang Q (2021) Gut organoid as a new platform to study alginate and chitosan mediated PLGA nanoparticles for drug delivery. Mar Drug 19:1–15
Du X, Liu Y, Wang X, Yan H, Wang L, Qu L, Kong D, Qiao M, Wang L (2019) Injectable hydrogel composed of hydrophobically modified chitosan/oxidized-dextran for wound healing. Mater Sci Eng C 104:109930
Guo W, Yang M, Liu S, Zhang X, Chen Y (2021) Chitosan/polyvinyl alcohol/tannic acid multiple network composite hydrogel: preparation and characterization. Iran Polym J 30:1159–1168
Wang Q, Du Y, Fan L, Hui L, Xiaohui W (2003) Structures and properties of chitosan-starch-sodium benzoate blend films. Wuhan Daxue Xuebao (Lixue Ban)/J Wuhan Univ (Natural Sci Ed). 49:725
Mu M, Li X, Tong A, Guo G (2019) Multi-functional chitosan-based smart hydrogels mediated biomedical application. Expert Opin Drug Deliv 16:239–250
Zhang W, Zhao M, Gao Y, Cheng X, Liu X, Tang S, Peng Y, Wang N, Hu D, Peng H, Zhang J, Wang Q (2022) Biomimetic erythrocytes engineered drug delivery for cancer therapy. Chem Eng J 433:133498
Singha I, Basu A (2022) Chitosan based injectable hydrogels for smart drug delivery applications. Sensors Int 3:100168
Wang Q, Zhang N, Hu X, Yang J, Du Y (2008) Chitosan/polyethylene glycol blend fibers and their properties for drug controlled release. J Biomed Mater Res, Part A 85:881–887
Veerapandian B, Shanmugam SR, Varadhan S, Sarwareddy KK, Mani KP (2020) Levan production from sucrose using chicken feather peptone as a low cost supplemental nutrient source. Carbohydr Polym 227:115361
Zhang X, Yang Y, Yao J, Shao Z, Chen X (2014) Strong collagen hydrogels by oxidized dextran modification. ACS Sustain Chem Eng 2:1318–1324
Kazak Sarilmiser H, Toksoy Oner E (2014) Investigation of anti-cancer activity of linear and aldehyde-activated levan from Halomonas smyrnensis AAD6T. Biochem Eng J 92:28–34
Janarthanan G, Tran HN, Cha E, Lee C, Das D, Noh I (2020) 3D printable and injectable lactoferrin-loaded carboxymethyl cellulose-glycol chitosan hydrogels for tissue engineering applications. Mater Sci Eng C 113:111008
Zhang Y, Huo M, Zhou J, Zou A, Li W, Yao C, Xie S (2010) DDSolver: An add-in program for modeling and comparison of drug dissolution profiles. AAPS J 12:263–271
Ekenna IC, Abali SO (2022) Comparison of the use of kinetic model plots and DD solver software to evaluate the drug release from Griseofulvin tablets. J Drug Deliv Ther 12:5–13
Huang Y, Zhang X, Wu A, Xu H (2016) An injectable nano-hydroxyapatite (n-HA)/glycol chitosan (G-CS)/hyaluronic acid (HyA) composite hydrogel for bone tissue engineering. RSC Adv 6:33529–33536
Manzoor A, Dar AH, Pandey VK, Shams R, Khan S, Panesar PS, Kennedy JF, Fayaz U, Khan SA (2022) Recent insights into polysaccharide-based hydrogels and their potential applications in food sector: a review. Int J Biol Macromol 213:987–1006
Chen MH, Wang LL, Chung JJ, Kim YH, Atluri P, Burdick JA (2017) Methods to assess shear-thinning hydrogels for application as injectable biomaterials. ACS Biomater Sci Eng 3:3146–3160
Kocen R, Gasik M, Gantar A, Novak S (2017) Viscoelastic behaviour of hydrogel-based composites for tissue engineering under mechanical load. Biomed Mater 12:025004
Fan Z, Liu B, Wang J, Zhang S, Lin Q, Gong P, Ma L, Yang S (2014) A novel wound dressing based on Ag/graphene polymer hydrogel: effectively kill bacteria and accelerate wound healing. Adv Funct Mater 24:3933–3943
Feng W, Wang Z (2022) Shear-thinning and self-healing chitosan-graphene oxide hydrogel for hemostasis and wound healing. Carbohydr Polym 294:119824
Mitra T, Manna PJ, Raja STK, Gnanamani A, Kundu PP (2015) Curcumin loaded nano graphene oxide reinforced fish scale collagen – a 3D scaffold biomaterial for wound healing applications. RSC Adv 5:98653–98665
Wu Y, Wang H, Gao F, Xu Z, Dai F, Liu W (2018) An injectable supramolecular polymer nanocomposite hydrogel for prevention of breast cancer recurrence with theranostic and mammoplastic functions. Adv Funct Mater 28:1–12
Mahmood K, Zia KM, Zuber M, Salman M, Anjum MN (2015) Recent developments in curcumin and curcumin based polymeric materials for biomedical applications: a review. Int J Biol Macromol 81:877–890
Demirci T, Hasköylü ME, Eroğlu MS, Hemberger J, Toksoy Öner E (2020) Levan-based hydrogels for controlled release of Amphotericin B for dermal local antifungal therapy of Candidiasis. Eur J Pharm Sci 145:105255
Ali A, Ajaz M, Tahir M, Ruqia U, Farid-ul-haq M, Tabassum T, Muhammad G, Zajif S, Hussain I, Erum A (2023) Synthesis, characterization, and acute toxicity of pH-responsive Salvia spinosa mucilage-co-acrylic acid hydrogel: a smart excipient for drug release applications. React Funct Polym 182:105466
Saeedi M, Reza M, Vahidi O (2023) Chitosan/glycyrrhizic acid hydrogel: preparation, characterization, and its potential for controlled release of gallic acid. Int J Biol Macromol 231:123197
Acknowledgements
The first author Mrs. Bhuvaneshwari Veerapandian sincerely thanks CSIR for the financial support through the SRF fellowship (Direct SRF/09/1095(0061)/2020 EMR-I). Dr Thirupathi Kumara Raja Selvaraj shows his sincere thanks to SERB-SRG for the financial support (SRG/2021/00562). All the authors sincerely thank the Department of Science & Technology and SASTRA Deemed University for support through the FIST program (Grant: SR/FST/ET-1/2020/614(C)).
Funding
The study was supported by Council of Scientific & Industrial Research, SRF/09/1095(0061)/2020 EMR-I, Bhuvaneshwari Veerapandian, Science and Engineering Research Board, SRG/2021/00562, Thirupathi Kumara Raja, and Department of Science and Technology, Government of India, India, SR/FST/ET-1/2020/614(C), Ponnusami Venkatachalam.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Veerapandian, B., Selvaraj, T.K., Shanmugam, S.R. et al. In-vitro drug release and stability assessment of tailored levan–chitosan biocomposite hydrogel. Iran Polym J 33, 11–23 (2024). https://doi.org/10.1007/s13726-023-01229-x
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s13726-023-01229-x