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Projeto de investigação
Smart hydrogel-based Injectable systems for breast cancer theranostics
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Injectable Composite Systems of Gellan Gum:Alginate Microparticles in Pluronic Hydrogels for Bioactive Cargo Controlled Delivery
Publication . Carrêlo, Henrique; Escoval, André R.; Soares, Paula I. P.; Borges, João P.; Cidade, Maria Teresa; CENIMAT-i3N - Centro de Investigação de Materiais (Lab. Associado I3N); DCM - Departamento de Ciência dos Materiais; MDPI - Multidisciplinary Digital Publishing Institute
Due to the high complexity of some treatments, there is a need to develop drug-delivery systems that can release multiple drugs/bioactive agents at different stages of treatment. In this study, a thermoresponsive injectable dual-release system was developed with gellan gum/alginate microparticles (GG:Alg) within a thermoresponsive Pluronic hydrogel composed of a mixture of Pluronic F127 and F68. The increase in F68 ratio and decrease in F127 lead to higher transition temperatures. The addition of the GG:Alg microparticles decreased the transition temperatures with a linear tendency. In Pluronic aqueous solutions (20 wt.%), the F127:F68 ratios of 16:4 and 17:3 (wt.%:wt.%) and the addition of microparticles (up to 15 wt.%) maintained the sol–gel transition temperatures within a suitable range (between 25 °C and 37 °C). Microparticles did not hinder the injectability of the system in the sol phase. Methylene blue was used as a model drug to evaluate the release mechanisms from microparticles, hydrogel, and composite system. The hydrogel delayed the release of methylene blue from the microparticles. The hydrogel loaded with methylene blue released at a faster rate than the microparticles within the hydrogel, thus demonstrating a dual-release profile.
Effect of ScCO2 on the decontamination of PECs-based cryogels
Publication . Bento, Cristiana S. A.; Carrêlo, Henrique; Alarico, Susana; Empadinhas, Nuno; de Sousa, Hermínio C.; Teresa Cidade, Maria; Braga, Mara E. M.; CENIMAT-i3N - Centro de Investigação de Materiais (Lab. Associado I3N); DCM - Departamento de Ciência dos Materiais; Elsevier
Biopolymers present ideal properties to be used in wound dressing solutions. By mixing two oppositely charged macromolecules it is possible to form polyelectrolyte complex (PEC) based cryogels using lyophilization. Their application in the biomedical field is limited due to their sterilization requirements, as conventional methods compromise their physicochemical properties. ScCO2 appears as an alternative method for decontamination. This work assessed several cryogel PEC formulations, chitosan-pectin, gelatine-xanthan gum and alginate-gelatine. PEC formation was confirmed by FTIR and rheological analysis. While steam sterilization compromised cryogels’ chemical and morphological properties, decontamination with scCO2 proved to be a promising method for decontamination of PEC-cryogels, because, similarly to what is observed with hydrogen peroxide, it does not compromise their physicochemical properties.
Injectable composite systems based on microparticles in hydrogels for bioactive cargo controlled delivery
Publication . Carrêlo, Henrique; Soares, Paula I. P.; Borges, João Paulo; Cidade, Maria Teresa; CENIMAT-i3N - Centro de Investigação de Materiais (Lab. Associado I3N); DCM - Departamento de Ciência dos Materiais; MDPI - Multidisciplinary Digital Publishing Institute
Engineering drug delivery systems (DDS) aim to release bioactive cargo to a specific site within the human body safely and efficiently. Hydrogels have been used as delivery matrices in different studies due to their biocompatibility, biodegradability, and versatility in biomedical purposes. Microparticles have also been used as drug delivery systems for similar reasons. The combination of microparticles and hydrogels in a composite system has been the topic of many research works. These composite systems can be injected in loco as DDS. The hydrogel will serve as a barrier to protect the particles and retard the release of any bioactive cargo within the particles. Additionally, these systems allow different release profiles, where different loads can be released sequentially, thus allowing a synergistic treatment. The reported advantages from several studies of these systems can be of great use in biomedicine for the development of more effective DDS. This review will focus on in situ injectable microparticles in hydrogel composite DDS for biomedical purposes, where a compilation of different studies will be analysed and reported herein.
Gellan Gum/Alginate Microparticles as Drug Delivery Vehicles
Publication . Carrêlo, Henrique; Cidade, Maria Teresa; Borges, João Paulo; Soares, Paula; CENIMAT-i3N - Centro de Investigação de Materiais (Lab. Associado I3N); DCM - Departamento de Ciência dos Materiais; Molecular Diversity Preservation International (MDPI)
Gellan gum is a biocompatible and easily accessible polysaccharide with excellent properties to produce microparticles as drug delivery systems. However, the production methods often fail in reproducibility, compromising the translational potential of such systems. In this work, the production of gellan gum-based microparticles was optimized using the coaxial air flow method, and an inexpensive and reproducible production method. A design of experiments was used to identify the main parameters that affect microparticle production and optimization, focusing on diameter and dispersibility. Airflow was the most significant factor for both parameters. Pump flow affected the diameter, while the gellan gum/alginate ratio affected dispersibility. Microparticles were revealed to be sensitive to pH with swelling, degradation, and encapsulation efficiency affected by pH. Using methylene blue as a model drug, higher encapsulation, and swelling indexes were obtained at pH 7.4, while a more pronounced release occurred at pH 6.5. Within PBs solutions, the microparticles endured up to two months. The microparticle release profiles were studied using well-known models, showing a Fickian-type release, but with no alteration by pH. The developed microparticles showed promising results as drug-delivery vehicles sensitive to pH.
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Fundação para a Ciência e a Tecnologia
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SFRH/BD/144986/2019