Curcumin-loaded chitosan thermosensitive hydrogel with sustained release for periodontal applications: an in vitro evaluation
DOI:
https://doi.org/10.1590/Keywords:
Thermosensitive hydrogel, Localized periodontal drug delivery, Sustained-release biomaterials, Antibiofilm activity, PeriodontitisAbstract
Objective: Thermosensitive hydrogels have emerged as promising localized drug delivery systems for periodontal therapy. Curcumin possesses anti-inflammatory and antimicrobial properties but is limited by its poor solubility and bioavailability. This study aimed to develop and evaluate a curcumin-loaded chitosan thermosensitive hydrogel for periodontal application. Methodology: This in vitro experimental study included five groups as positive controls, negative control, blank chitosan hydrogel, free curcumin, curcumin-loaded hydrogel, and chlorhexidine (0.12%). The hydrogel was formulated using chitosan and β-glycerophosphate and was characterized for thermosensitive gelation and injectability. Drug release was assessed using dialysis. Cytocompatibility was evaluated in human gingival fibroblasts (HGF-1) using the MTT assay at 24, 48, and 72 h. The anti-inflammatory activity was assessed by measuring the levels of TNF-α and IL-1β in LPS-stimulated cells. Antibacterial activity (MIC/MBC) and antibiofilm efficacy were tested against Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans. Data were analyzed using ANOVA with the appropriate post-hoc tests (p<0.05). Results: The curcumin-loaded hydrogel showed high cell viability (>90%) and significantly reduced TNF-α and IL-1β levels when compared with free curcumin. It demonstrated improved antibiofilm activity (∼74–79%) and lower MIC values than free curcumin, although slightly less effective than chlorhexidine. A sustained drug release profile (∼81.6% at 14 days) following Korsmeyer–Peppas kinetics was observed. Conclusion: The curcumin-loaded chitosan thermosensitive hydrogel showed improved biological performance and sustained release when compared with free curcumin, suggesting its potential as a localized periodontal drug delivery system. Further in vivo studies are required to validate these findings.
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References
1- Slots J. Periodontitis: facts, fallacies and the future. Periodontol 2000. 2017;75(1):7-23. doi: 10.1111/prd.12221
» https://doi.org/10.1111/prd.12221
2-risko CH. Nonsurgical periodontal therapy. Periodontol 2000. 2001;25:77–88. doi: 10.1034/j.1600-0757.2001.22250106.x
» https://doi.org/10.1034/j.1600-0757.2001.22250106.x
3- Verma SK, Kumari S, Kumari N, Priyadarshi M, Verma A, Priyank H, et al. Clinical outcomes of laser-assisted non-surgical periodontal therapy for chronic periodontitis treatment. Bioinformation. 2025;21(8):2789–94. doi: 10.6026/973206300212789
» https://doi.org/10.6026/973206300212789
4- Fan R, Cheng Y, Wang R, Zhang T, Zhang H, Li J, et al. Thermosensitive hydrogels and advances in their application in disease therapy. Polymers (Basel). 2022;14(12):2379. doi: 10.3390/polym14122379
» https://doi.org/10.3390/polym14122379
5- Li M, Lv J, Yang Y, Cheng G, Guo S, Liu C, et al. Advances of hydrogel therapy in periodontal regeneration: a materials perspective review. Gels. 2022;8(10):624. doi: 10.3390/gels8100624
» https://doi.org/10.3390/gels8100624
6- Ahmadi F, Oveisi Z, Samani SM, Amoozgar Z. Chitosan-based hydrogels: characteristics and pharmaceutical applications. Res Pharm Sci. 2015;10(1):1-16.
7- Boyapati R, Dhulipalla R, Kolaparthy L, Vintha J. Exploring curcumin's efficacy in the management of periodontal disease: an umbrella review. J Indian Soc Periodontol. 2025;29(3):241-8. doi:10.4103/jisp.jisp_100_25
» https://doi.org/10.4103/jisp.jisp_100_25
8- Sohn SI, Priya A, Balasubramaniam B, Muthuramalingam P, Sivasankar C, Selvaraj A, et al. Biomedical applications and bioavailability of curcumin: an updated overview. Pharmaceutics. 2021;13(12):2102. doi: 10.3390/pharmaceutics13122102
» https://doi.org/10.3390/pharmaceutics13122102
9- Liu C, Chen Y, Bai H, Niu Y, Wu Y. Characterization and application of in situ curcumin/ZNP hydrogels for periodontitis treatment. BMC Oral Health. 2024;24(1):395. doi: 10.1186/s12903-024-04054-7
» https://doi.org/10.1186/s12903-024-04054-7
10- Zhu Y, Ali A, Santos GM, Franciscon JP, Molon RS, Goh C, et al. A chitosan-based hydrogel to modulate immune cells and promote periodontitis healing in the high-fat diet-induced periodontitis rat model. Acta Biomater. 2025;200:452-63. doi: 10.1016/j.actbio.2025.05.034
» https://doi.org/10.1016/j.actbio.2025.05.034
11- Zhang G, Zhang M, Feng Q, Wang R, Mei H, Xing K, et al. Supramolecular composite hydrogel loaded with CaF2 nanoparticles promotes recovery of periodontitis bone resorption. ACS Appl Mater Interfaces. 2024;16(35):45929-5947. doi: 10.1021/acsami.4c07210
» https://doi.org/10.1021/acsami.4c07210
12- Diomede F, Fonticoli L, Guarnieri S, Della Rocca Y, Rajan TS, Fontana A, et al. The effect of liposomal curcumin as an anti-inflammatory strategy on lipopolysaccharide from Porphyromonas gingivalis-treated endothelial committed neural crest derived stem cells: morphological and molecular mechanisms. Int J Mol Sci. 2021;22(14):7534. doi: 10.3390/ijms22147534
» https://doi.org/10.3390/ijms22147534
13- Sinjari B, Pizzicannella J, D’Aurora M, Zappacosta R, Gatta V, Fontana A, et al. Curcumin/liposome nanotechnology as delivery platform for anti-inflammatory activities via NFκB/ERK/pERK pathway in human dental pulp treated with 2-hydroxyethyl methacrylate (HEMA). Front Physiol. 2019;10:633. doi: 10.3389/fphys.2019.00633
» https://doi.org/10.3389/fphys.2019.00633
14- Pakzad Y, Ganji F. Thermosensitive hydrogel for periodontal application: in vitro drug release, antibacterial activity and toxicity evaluation. J Biomater Appl. 2016;30(7):919-29. doi: 10.1177/0885328215614191
» https://doi.org/10.1177/0885328215614191
15- Gonciarz W, Balcerczak E, Brzeziński M, Jeleń A, Pietrzyk-Brzezińska AJ, Narayanan VHB, et al. Chitosan-based formulations for therapeutic applications: a recent overview. J Biomed Sci. 2025;32(1):62. doi: 10.1186/s12929-025-01161-7
» https://doi.org/10.1186/s12929-025-01161-7
16- Tabanelli R, Brogi S, Calderone V. Improving curcumin bioavailability: current strategies and future perspectives. Pharmaceutics. 2021;13(10):1715. doi: 10.3390/pharmaceutics13101715
» https://doi.org/10.3390/pharmaceutics13101715
17- Liu JX, Werner J, Kirsch T, Zuckerman JD, Virk MS. Cytotoxicity evaluation of chlorhexidine gluconate on human fibroblasts, myoblasts, and osteoblasts. J Bone Jt Infect. 2018;3(4):165-172. doi: 10.7150/jbji.26355
» https://doi.org/10.7150/jbji.26355
18- Cunha G, D'Angieri Saugo G, Gabrielli MA, Barbeiro CO, Almeida LY, Bufalino A, et al. Cytotoxicity evaluation of chlorhexidine and Blue®M applied to human gingival fibroblasts (HGF-1) and keratinocytes (NOK-SI): an in vitro study. J Stomatol Oral Maxillofac Surg. 2024;125(12 Suppl 2):101923. doi: 10.1016/j.jormas.2024.101923
» https://doi.org/10.1016/j.jormas.2024.101923
19- Liu M, Wang J, Song Z, Pei Y. Regulation mechanism of curcumin-mediated inflammatory pathways and its clinical application: a review. Front Pharmacol. 2025;16:1642248. doi: 10.3389/fphar.2025.1642248
» https://doi.org/10.3389/fphar.2025.1642248
20- Yang K, Han Q, Chen B, Zheng Y, Zhang K, Li Q, et al. Antimicrobial hydrogels: promising materials for medical applications. Int J Nanomedicine. 2018;13:2217–63. doi: 10.2147/IJN.S154748
» https://doi.org/10.2147/IJN.S154748
21- Gong C, Qi T, Wei X, Qu Y, Wu Q, Luo F, et al. Thermosensitive polymeric hydrogels as drug delivery systems. Curr Med Chem. 2013;20(1):79-94. doi: 10.2174/0929867311302010009
» https://doi.org/10.2174/0929867311302010009
22- Huang X, Ren F, Yang H, Bai X, Fang J, Wang J, et al. Cellulose-based hydrogel mitigates periodontitis with sustained release of curcumin. Int Dent J. 2025;75(Suppl 1):105013. doi: 10.1016/j.identj.2025.105013
» https://doi.org/10.1016/j.identj.2025.105013
23- Poppolo Deus F, Ouanounou A. Chlorhexidine in dentistry: pharmacology, uses, and adverse effects. Int Dent J. 2022;72(3):269-77. doi: 10.1016/j.identj.2022.01.005
» https://doi.org/10.1016/j.identj.2022.01.005
24- Ferreira S, Grenho L, Fernandes MH, Lima SA. Curcumin-loaded lipid nanoparticles: a promising antimicrobial strategy against Enterococcus faecalis in endodontic infections. Pharmaceutics. 2025;17(1):108. doi: 10.3390/pharmaceutics17010108
» https://doi.org/10.3390/pharmaceutics17010108
25- Ferreira S, Grenho L, Fernandes MH, Lima SA. Photoactivated curcumin-loaded lipid nanoparticles in hydrogel: a cutting-edge intracanal medicament for advanced endodontic therapy. Gels. 2025;11(5):308. doi: 10.3390/gels11050308
» https://doi.org/10.3390/gels11050308
26- Siepmann J, Peppas NA. Higuchi equation: derivation, applications, use and misuse. Int J Pharm. 2011;418(1):6-12. doi: 10.1016/j.ijpharm.2011.03.051
» https://doi.org/10.1016/j.ijpharm.2011.03.051
27- Dash M, Chiellini F, Ottenbrite RM, Chiellini E. Chitosan - a versatile semi-synthetic polymer in biomedical applications. Prog Polym Sci. 2011;36(8):981-1014. doi: 10.1016/j.progpolymsci.2011.02.001
» https://doi.org/10.1016/j.progpolymsci.2011.02.001
28- Barman M, Mahmood S, Augustine R, Hasan A, Thomas S, Ghosal K. Natural halloysite nanotubes/chitosan based bio-nanocomposite for delivering norfloxacin, an anti-microbial agent in sustained release manner. Int J Biol Macromol. 2020;162:1849-61. doi: 10.1016/j.ijbiomac.2020.08.060
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