O-carboxymethylchitosan hydrogel loaded with dexamethasone for intraocular use
Palavras-chave:
Biomaterials, Ophthalmology, Anti-inflammatory, CataractResumo
This study aimed to develop hydrogels from carboxymethyl chitosan (CMC), and carboxymethyl chitosan (CMC) with dexamethasone (DEX) for intraocular application, aiming to provide structural stability to the eye and attenuation of inflammatory processes. CMC hydrogels were prepared at concentrations of 0.5%, 1% and 2% (w/v) and incorporated with 10% (v/v) DEX. The samples were characterized by FT-IR spectroscopic, thermogravimetric analysis, injectability, rheology, and cytotoxicity. The results showed that the incorporation of DEX did not significantly alter the absorption bands and thermal behavior of the CMQ hydrogels. Injectability tests revealed that hydrogels with DEX require injection force similar to the commercial material. In rheological tests, pseudoplastic and linear viscoelastic behavior was identified. Cytotoxicity tests confirmed the biocompatibility of the hydrogels. These results demonstrate that the developed hydrogels have properties suitable for biomedical applications, especially aimed at the ophthalmological context.
Downloads
Referências
AHIRRAO, S. P.; BHAMBERE, D. S.; AGIWALE, B.; ALGAT, S.; ZOMAN, D.; CHAUDHARI, V. pH sensitive in-situ gel for ophthalmic delivery of ofloxacin and dexamethasone sodium phosphate: Formulation, development, and evaluation. J Materials Today: Proceedings, 2023.
ALLEN, L.; ANSEL, H. C. Ansel's pharmaceutical dosage forms and drug delivery systems. Lippincott Williams & Wilkins, 2013. ISBN 1451188765.
CHEN, X.-G.; PARK, H.-J. Chemical characteristics of O-carboxymethyl chitosans related to the preparation conditions. Carbohydrate Polymers, v. 53, n. 4, p. 355-359, 2003.
DATTA, S.; CANO, M.; EBRAHIMI, K.; WANG, L.; HANDA, J. T. J. P. I. R.; RESEARCH, E. The impact of oxidative stress and inflammation on RPE degeneration in non-neovascular AMD. Progress in retinal eye research, v. 60, p. 201-218, 2017.
DE LACERDA BUKZEM, A.; DOS SANTOS, D. M.; LEITE, I. S.; INADA, N. M.; CAMPANA-FILHO, S. P. Tuning the properties of carboxymethylchitosan-based porous membranes for potential application as wound dressing. J International Journal of Biological Macromolecules, v. 166, p. 459-470, 2021.
ENOCH, K.; SOMASUNDARAM, A. A. Rheological insights on Carboxymethyl cellulose hydrogels. International Journal of Biological Macromolecules, v. 253, p. 127481, 2023.
FIGUEIRÊDO, E. S. D.; MACEDO, A. C. D.; FIGUEIRÊDO, P. F. R. D.; FIGUEIRÊDO, R. S. D. J. A. B. D. O. Aplicações oftalmológicas do ácido hialurônico. Arquivos Brasileiros de Oftalmologia, v. 73, p. 92-95, 2010.
GALDINO, T. P.; OLIVEIRA, L. C. D.; LIMA, E. P. N.; FARIAS, R. Í. R.; JESUS, R. A. D.; QUEIROZ, S. F. A. M. D.; SANTOS, A. C. D. Q.; FOOK, M. V. L. Synthesis and characterization of O-Carboxymethylchitosan as an alternative to the use of Hyaluronic Acid. Research, Society and Development, v. 11, n. 5, p. e5011527634, 2022.
HADI, Z.; NAVARCHIAN, A. H.; RAFIENIA, M. Synthesis of pH-responsive carboxymethyl chitosan for encapsulating tetracycline-HCl: Morphology, drug release behavior and antibacterial activity of microcapsules. Journal of Drug Delivery Science and Technology, v. 84, p. 104462, 2023.
HALIMI, C.; MONTEMBAULT, A.; GUERRY, A.; DELAIR, T.; VIGUIER, E.; FULCHIRON, R.; DAVID, L. Chitosan solutions as injectable systems for dermal filler applications: Rheological characterization and biological evidence. In: 2015 37th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC), IEEE, p.2596-2599, 2015.
HALIMI, C.; MONTEMBAULT, A.; GUERRY, A.; DELAIR, T.; VIGUIER, E.; FULCHIRON, R.; DAVID, L. Chitosan solutions as injectable systems for dermal filler applications: Rheological characterization and biological evidence. Annu Int Conf IEEE Eng Med Biol Soc, v. 2015, p. 2596-9, 2015.
HAN, X.; LI, G.; YOU, S.; SHEN, M.; XU, Y.; YANG, H.; LU, C.; ZHANG, M.; FANG, J.; ZHOU, Q.; YAO, Q. Injectable bio-multifunctional hyaluronic acid-based hydrogels loaded with poly ADP-ribose polymerase inhibitors for ovarian cancer therapy. International Journal of Biological Macromolecules, p. 132275, 2024.
HAO, Y.; ZHAO, W.; ZHANG, H.; ZHENG, W.; ZHOU, Q. Carboxymethyl chitosan-based hydrogels containing fibroblast growth factors for triggering diabetic wound healing. Carbohydrate Polymers, v. 287, p. 119336, 2022.
HUNT, J. A.; CHEN, R.; VAN VEEN, T.; BRYAN, N. Hydrogels for tissue engineering and regenerative medicine. Journal of Materials Chemistry B, v. 2, n. 33, p. 5319-5338, 2014.
KŁOSIŃSKI, K. K.; WACH, R. A.; GIREK-BĄK, M. K.; ROKITA, B.; KOŁAT, D.; KAŁUZIŃSKA-KOŁAT, Ż.; KŁOSIŃSKA, B.; DUDA, Ł.; PASIEKA, Z. W. Biocompatibility and Mechanical Properties of Carboxymethyl Chitosan Hydrogels. Polymers (Basel). 15 2023.
KONG, H. J.; WONG, E.; MOONEY, D. J. Independent control of rigidity and toughness of polymeric hydrogels. Macromolecules, v. 36, n. 12, p. 4582-4588, 2003.
KWITKO, S. Endotélio e cirurgia da catarata: grandes desafios. J Arquivos Brasileiros de Oftalmologia v. 63, p. 235-239, 2000.
LADEIRA, N. M. B.; DONNICI, C. L.; DE MESQUITA, J. P.; PEREIRA, F. V. Preparation and characterization of hydrogels obtained from chitosan and carboxymethyl chitosan. Journal of Polymer Research, v. 28, n. 9, p. 335, 2021.
LUCIO, D.; ZORNOZA, A.; MARTÍNEZ-OHÁRRIZ, M. C. Role of Microstructure in Drug Release from Chitosan Amorphous Solid Dispersions. International Journal of Molecular Sciences, v. 23, n. 23, p. 15367, 2022.
LUCIO, D.; ZORNOZA, A.; MARTÍNEZ-OHÁRRIZ, M. C. J. I. J. O. P. Influence of chitosan and carboxymethylchitosan on the polymorphism and solubilisation of diflunisal. International Journal of Pharmaceutics, v. 467, n. 1-2, p. 19-26, 2014.
MA, C.; WANG, Y.; JIANG, Z.; CAO, Z.; YU, H.; HUANG, G.; WU, Q.; LING, F.; ZHUANG, Z.; WANG, H.; ZHENG, J.; WU, J. Wide-range linear viscoelastic hydrogels with high mechanical properties and their applications in quantifiable stress-strain sensors. Chemical Engineering Journal, v. 399, p. 125697, 2020.
MATADH, A. V.; JAKKA, D.; PRAGATHI, S. G.; POORNIMA, K.; SHIVAKUMAR, H. N.; MURTHY, R. N.; RANGAPPA, S.; SHIVANNA, M.; MURTHY, S. N. Polymer coated polymeric microneedles for intravitreal delivery of dexamethasone. Experimental Eye Research, v. 231, p. 109467, 2023.
MOHSENI, M.; SHOKROLLAHI, P.; BARZIN, J. Gelatin/O-carboxymethyl chitosan injectable self-healing hydrogels for ibuprofen and naproxen dual release. International Journal of Biological Macromolecules, v. 263, p. 130266, 2024.
NAIR, R.; ROY CHOUDHURY, A. Synthesis and rheological characterization of a novel shear thinning levan gellan hydrogel. International Journal of Biological Macromolecules, v. 159, p. 922-930, 2020.
SAFA, B. N.; READ, A. T.; ETHIER, C. R. Assessment of the viscoelastic mechanical properties of the porcine optic nerve head using micromechanical testing and finite element modeling. Acta Biomaterialia, v. 134, p. 379-387, 2021.
SANTOS, W. M.; NÓBREGA, F. P.; ANDRADE, J. C.; ALMEIDA, L. F.; CONCEIÇÃO, M. M.; MEDEIROS, A. C. D.; MEDEIROS, F. D. Pharmaceutical compatibility of dexamethasone with excipients commonly used in solid oral dosage forms. Journal of Thermal Analysis and Calorimetry, v. 145, n. 2, p. 361-378, 2021.
SHINDE, S.; CHOUDHARY, K.; RANGU, V. Ophtalmic viscosurgical devices. Int. J. Adv. Res., v. 11, n. 02, p. 328-332, 2023.