Hidrogéis sustentáveis de sulfato de condroitina para liberação controlada e ambientalmente segura de fármacos: síntese, caracterização e responsividade ao pH

Autores/as

DOI:

https://doi.org/10.17765/2176-9192.2026v28e14248

Palabras clave:

Liberação controlada, pH-responsivo, Cólon, Biomateriais

Resumen

Hidrogéis à base de sulfato de condroitina (CS) têm se destacado como plataformas sustentáveis para liberação controlada de fármacos, devido à biocompatibilidade, biodegradabilidade e potencial de reduzir impactos ambientais. A combinação de CS com polímeros naturais ou sintéticos permite produzir matrizes inteligentes sensíveis ao pH, capazes de modular a liberação em ambientes fisiológicos específicos. Esta revisão sistemática de 50 estudos demonstrou que hidrogéis de CS constituem sistemas promissores, com perfis de segurança favoráveis e desempenho ajustável. A síntese ocorre majoritariamente por polimerização via radicais livres, empregando agentes reticulantes como etilenoglicol dimetacrilato (EGDMA) e N,N’-metileno-bisacrilamida (MBA). Os hidrogéis apresentam resposta consistente ao pH, com maior intumescimento e liberação em pH fisiológico (7,4) do que em condições ácidas (1,2), comportamento atribuído à protonação e desprotonação de grupos carboxílicos e sulfato que alteram densidade de carga e repulsão eletrostática. As durações de liberação variam de 36–72 horas para fármacos anti-inflamatórios a mais de seis semanas para terapias oncológicas catiônicas, com cinéticas descritas principalmente por mecanismos de difusão não Fickianos. Quanto à segurança ambiental, a evidência permanece limitada. Ensaios de citotoxicidade reportam viabilidade celular superior a 94%, e testes in vivo em coelhos indicam baixa toxicidade. A complexação com CS melhora a biocompatibilidade de polímeros sintéticos e estudos de biodegradação mostram degradação lenta em tampão fisiológico. Apesar disso, avaliações abrangentes de impacto ambiental, métricas de química verde e indicadores explícitos de sustentabilidade não foram relatados, representando uma lacuna relevante para conclusões mais robustas sobre a sustentabilidade desses hidrogéis.

Biografía del autor/a

Jacqueline Maria Lopes Marin, Universidade Estadual de Maringá

Universidade Estadual de Maringá, Maringá, Paraná, Brasil

Jakelline Braga dos Santos, UniCesumar

Programa de Pós-graduação em Tecnologias Limpas, Universidade Cesumar, Maringá, Paraná, Brasil.

Aline Lopes, Unicesumar/ PPGTL

Doutora em ecologia

Mônica Elisa Buttow, Unicesumar

Bióloga pela Universidade Estadual de Maringá, mestre em Biotecnologia pela Universidade Federal de Santa Catarina.

Citas

ALI, Akhtar et al. Preparation and in vitro evaluation of Chondroitin sulfate and carbopol based mucoadhesive controlled release polymeric composites of Loxoprofen using factorial design. European Polymer Journal, v. 121, p. 109312, 2019.

ALINEJAD, Yasaman et al. An injectable chitosan/chondroitin sulfate hydrogel with tunable mechanical properties for cell therapy/tissue engineering. International journal of biological macromolecules, v. 113, p. 132-141, 2018.

BARKAT, Kashif et al. Oxaliplatin?loaded crosslinked polymeric network of chondroitin sulfate?co?poly (methacrylic acid) for colorectal cancer: Its toxicological evaluation. Journal of Applied Polymer Science, v. 134, n. 38, p. 45312, 2017.

BEDINI, Emiliano et al. Microbiological-chemical sourced chondroitin sulfates protect neuroblastoma SH-SY5Y cells against oxidative stress and are suitable for hydrogel-based controlled release. Antioxidants, v. 10, n. 11, p. 1816, 2021.

FAHAD, Muhammad et al. Fabrication and evaluation of chondroitin sulfate based hydrogels loaded with chitosan nanoparticles for oral delivery of vildagliptin. International Journal of Biological Macromolecules, v. 290, p. 139011, 2025.

FAJARDO, André R. et al. Hydrogel based on an alginate–Ca 2+/chondroitin sulfate matrix as a potential colon-specific drug delivery system. Rsc Advances, v. 2, n. 29, p. 11095-11103, 2012.

FAN, Ming et al. Covalent and injectable chitosan-chondroitin sulfate hydrogels embedded with chitosan microspheres for drug delivery and tissue engineering. Materials Science and Engineering: C, v. 71, p. 67-74, 2017.

GUAN, Xiangheng; YAO, Haochen; WU, Jinglei. Photocrosslinkable hydrogel of ibuprofen?chitosan methacrylate modulates inflammatory response. Journal of Biomedical Materials Research Part A, v. 112, n. 11, p. 2001-2017, 2024.

KHALID, Ikrima et al. Synthesis and evaluation of chondroitin sulfate based hydrogels of loxoprofen with adjustable properties as controlled release carriers. Carbohydrate polymers, v. 181, p. 1169-1179, 2018.

LIANG, Yongping et al. pH-responsive injectable hydrogels with mucosal adhesiveness based on chitosan-grafted-dihydrocaffeic acid and oxidized pullulan for localized drug delivery. Journal of colloid and interface science, v. 536, p. 224-234, 2019.

LIU, Sixian et al. Injectable and self-healing hydrogel based on chitosan-tannic acid and oxidized hyaluronic acid for wound healing. ACS Biomaterials Science & Engineering, v. 8, n. 9, p. 3754-3764, 2022.

NAEEM, Saba et al. Fabrication of pH responsive hydrogel blends of chondroitin sulfate/pluronic F-127 for the controlled release of ketorolac: its characterization and acute oral toxicity study. Drug Development and Industrial Pharmacy, v. 48, n. 11, p. 611-622, 2022.

NEMADE, Mahesh S.; CHAUDHARI, Rajesh. Y.; PATIL, Vijay R. Novel approaches to colon-targeted drug delivery system: A Review. RRJPPS, v. 3, n. 2, p. 63-69, 2014.

NOREEN, Sobia et al. Novel thiol-functionalized hyaluronic acid-based pH-responsive hydrogel: A promising mucoadhesive drug delivery approach toward the treatment of colorectal cancer. Colloids and Surfaces B: Biointerfaces, p. 114805, 2025.

OPREA, Ana-Maria et al. Cellulose/chondroitin sulfate hydrogels: Synthesis, drug loading/release properties and biocompatibility. Cellulose Chemistry & Technology, v. 44, n. 9, p. 369, 2010.

ORNELL, Kimberly J. et al. Controlling methacryloyl substitution of chondroitin sulfate: injectable hydrogels with tunable long-term drug release profiles. Journal of Materials Chemistry B, v. 7, n. 13, p. 2151-2161, 2019.

QAISER, Rubina et al. Development of chondroitin sulfate-based mucoadhesive interpenetrating polymeric hydrogels of captopril with adjustable properties as gastro-retentive sustained drug release carriers. Polymer Bulletin, v. 81, n. 6, p. 5267-5293, 2024.

RAY, Somasree. Advanced colon-specific delivery systems for treating local disorders. In: Polysaccharide carriers for drug delivery. Woodhead Publishing, 2019. p. 737-762.

SHAH, Syed Ahmed et al. Improved drug delivery and accelerated diabetic wound healing by chondroitin sulfate grafted alginate-based thermoreversible hydrogels. Materials Science and Engineering: C, v. 126, p. 112169, 2021.

SIMÃO, Andressa Renatta et al. pH-responsive hybrid hydrogels: Chondroitin sulfate/casein trapped silica nanospheres for controlled drug release. International journal of biological macromolecules, v. 148, p. 302-315, 2020.

SRUJANA, K.; HEMALATHA, B.; PADMALATHA, K. A Review on Colon Targeted Drug Delivery System. Asian Journal of Pharmacy and Technology, v. 13, n. 1, p. 57-64, 2023.

SUHAIL, Muhammad et al. Fabrication and in vitro evaluation of pH-sensitive polymeric hydrogels as controlled release carriers. Gels, v. 7, n. 3, p. 110, 2021.

SUHAIL, Muhammad et al. In vitro evaluation of smart and pH-sensitive chondroitin sulfate/sodium polystyrene sulfonate hydrogels for controlled drug delivery. Gels, v. 8, n. 7, p. 406, 2022a.

SUHAIL, Muhammad et al. Preparation of chondroitin sulfate and polyvinyl alcohol hydrogels as drug carriers. Applied Surface Science Advances, v. 18, p. 100478, 2023.

SUHAIL, Muhammad et al. Preparation of pH-responsive hydrogels based on chondroitin sulfate/alginate for oral drug delivery. Pharmaceutics, v. 14, n. 10, p. 2110, 2022b.

SUHAIL, Muhammad et al. Preparation, in vitro characterization, and cytotoxicity evaluation of polymeric pH-responsive hydrogels for controlled drug release. Pharmaceutics, v. 14, n. 9, p. 1864, 2022.

SUHAIL, Muhammad; WU, Pao-Chu; MINHAS, Muhammad Usman. Development and characterization of pH-sensitive chondroitin sulfate-co-poly (acrylic acid) hydrogels for controlled release of diclofenac sodium. Journal of Saudi Chemical Society, v. 25, n. 4, p. 101212, 2021.

YUAN, Fu-Zhen et al. Fabrication of injectable chitosan-chondroitin sulfate hydrogel embedding kartogenin-loaded microspheres as an ultrasound-triggered drug delivery system for cartilage tissue engineering. Pharmaceutics, v. 13, n. 9, p. 1487, 2021.

ZHAO, Changwen et al. Photo?cross?linked biodegradable thermo?and pH?responsive hydrogels for controlled drug release. Journal of applied polymer science, v. 123, n. 5, p. 2923-2932, 2012.

ZHONG, Huiling et al. Deferoxamine-loaded injectable chitosan-grafted chlorogenic acid/oxidized hyaluronic acid hybrid hydrogel with antibacterial, anti-inflammatory, and angiogenesis-promoting properties for diabetic wound repair. ACS Applied Materials & Interfaces, v. 16, n. 22, p. 28209-28221, 2024.

ZHU, Chongyang et al. A pH-sensitive hydrogel based on carboxymethylated konjac glucomannan crosslinked by sodium trimetaphosphate: Synthesis, characterization, swelling behavior and controlled drug release. International Journal of Biological Macromolecules, v. 232, p. 123392, 2023.

ZUCCA, Gaia et al. Chondroitin Sulphate-Chitosan Based Nanogels Loaded with Naringenin-?-Cyclodextrin Complex as Potential Tool for the Treatment of Diabetic Retinopathy: A Formulation Study. International Journal of Nanomedicine, p. 907-932, 2025.

Publicado

2026-05-25

Cómo citar

Marin, J. M. L., Santos, J. B. dos, Lopes, A., & Buttow, M. E. (2026). Hidrogéis sustentáveis de sulfato de condroitina para liberação controlada e ambientalmente segura de fármacos: síntese, caracterização e responsividade ao pH. Iniciação Científica Cesumar, 28, e14248. https://doi.org/10.17765/2176-9192.2026v28e14248

Número

Sección

Espaço Institucional de Pesquisa