resumo
Chitosan-based hydrogels hold promise as drug delivery systems for cancer therapy, but the poor mechanical properties often limit the biological application, requiring chemical cross-linking to improve sustained drug release. Besides, the addition of stimulus-responsiveness to chitosan requires chemical modifications that can further affect the gel properties. To overcome these challenges, in this work, a novel chitosan/alginate polyelectrolyte magnetic gel with tunable mechanical properties is developed by pH-triggered self-assembly. The gels could be prepared by a slow/fast pH decrease and blended with magnetic nanoparticles. Manganese-doped ferrite nanoparticles (similar to 10 nm) with suitable magnetic properties (>70 Am-2/kg) and high magnetic hyperthermia heating efficiency (ILP > 3 nHm(2)/kg) were synthesized via an amino acid-assisted oxidative hydrothermal method. The nanoparticles and self-assembly conditions of the polyelectrolyte complex enabled the tuning of the gels' properties, a fast gelation, and suitable mechanical properties for drug delivery. Notably, gels with a large storage modulus (up to 10 kPa) could be prepared at a low polymer concentration (<= 2 wt %). The magnetic gels enabled the sustained release of a hydrophilic chemotherapeutic drug model, 5-fluorouracil (5-FU), under mimetic physiological conditions, outperforming the hydrogels. Moreover, the drug release kinetics was synergistically enhanced under the combined effect of acidic conditions and magnetic hyperthermia. Hence, the developed self-assembled chitosan/alginate magnetic gel showed promising multifunctionality, combining tunable mechanical properties, magnetic hyperthermia capability, and sustained drug release. These features highlight the self-assembled chitosan/alginate magnetic gels as promising and versatile materials for localized and controlled drug delivery.
palavras-chave
CHITOSAN HYDROGELS; DRUG; DELIVERY; NANOPARTICLES; NANOCOMPOSITE; ALGINATE; PH; COMPLEX; TARGET
categoria
Science & Technology - Other Topics; Materials Science
autores
Veloso, SRS; Vazquez-Gonzalez, M; Ribeiro, MO; Hilliou, L; Amorim, CO; Amaral, VS; Correa-Duarte, MA; Castanheira, EMS
nossos autores
Carlos Amorim
Investigador Auxiliar
Vitor Brás Sequeira Amaral
Professor CatedráticoGrupos
G2 - Materiais Fotónicos, Eletrónicos e Magnéticos
G6 - Materiais Virtuais e Inteligência Artificial
agradecimentos
Financial support from Fundacaao para a Ciencia e a Tecnologia (FCT, Portugal) through UID/04650: Centro de Fisica das Universidades do Minho e do Porto (CF-UM-UP); UID/50011: CICECO Aveiro Institute of Materials and LA/P/0006/2020; UID/50025: Institute of Nanostructures, Nanomodelling and Nanofabrication-i3N (LISBOA-01-0247-FEDER-039985/POCI-01-0247-FEDER-039985) and LA/P/0037/2020 is acknowledged. This work was also supported by Ministerio de Ciencia e Innovacion de Espana (PID2020-113704RB-I00/AEI/10.13039/501100011033; TED2021-132101B-I00/AEI/10.13039/501100011033); European Union "NextGenerationEU"/PRTR, HORIZON-EIC-2022-PATHFINDER-CHALLENGES-01-06 and HORI-ZON-HLTH-2022-DISEASE-06-TWO-STAGE; and Xunta de Galicia (Centro Singular de Investigacioon de Galicia-Accreditation 2019-2022 ED431G 2019/06 and IN607A 2018/5).