Publicação
Smart hydrogel-based Injectable systems for breast cancer theranostics
| Resumo: | Breast cancer is the most common cancer in women. Current cancer treatments present severe side effects, decreasing the quality of life of patients. Thus, a critical challenge is to develop innovative drug delivery systems that are capable of delivering drugs/bioactive agents without causing toxic side effects. This Ph.D. thesis endeavors to meet this challenge by the development of an in situ injectable thermoresponsive drug delivery system tailored for cancer treatment. This system integrates polymeric magnetic microparticles within a thermoresponsive hydrogel, enabling localized drug delivery. The hydrogel performs a multifaceted role: transports the microparticles, and controls the drug release rate, thereby prolonging treatment effectiveness. The production of microparticles composed of Gellan Gum and Alginate was optimized using a coaxial air-flow method. These microparticles were engineered to include superparamagnetic iron oxide nanoparticles and methylene blue as a model drug, which served the dual purpose of enabling magnetic hyperthermia and controlled drug release. Microparticles were embedded within thermoresponsive systems, particularly Pluronic gels (F127 and F68 in varying ratios) and a chitosan hydrogel with β-Glycerophosphate. Notably, a Pluronic gel ratio of 17:3 (F127:F68) with 2 and 5 w/w% of microparticles demonstrated the ability to instantaneously shift from a sol state, at room temperature, to a gel state at body temperature. On the other hand, the chitosan hydrogel with microparticles exhibited a more prolonged transition from to the gel state at 37°C while demonstrating non- cytotoxicity to Vero cell lines, more rigid structure than the Pluronic hydrogel, and was able retard the drug release from the microparticles. In conclusion, the designed microparticle/hydrogel systems showed potential as drug delivery systems for future cancer therapies. Their development represents a significant stride towards more targeted and less harmful cancer treatments, with promising applications in other diseases as well. |
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| Autores principais: | Carrêlo, Henrique Nuno Curado |
| Assunto: | Hydrogels Microparticles Magnetic nanoparticles Breast cancer Rheology |
| Ano: | 2023 |
| País: | Portugal |
| Tipo de documento: | tese de doutoramento |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade Nova de Lisboa |
| Idioma: | inglês |
| Origem: | Repositório Institucional da UNL |
| Resumo: | Breast cancer is the most common cancer in women. Current cancer treatments present severe side effects, decreasing the quality of life of patients. Thus, a critical challenge is to develop innovative drug delivery systems that are capable of delivering drugs/bioactive agents without causing toxic side effects. This Ph.D. thesis endeavors to meet this challenge by the development of an in situ injectable thermoresponsive drug delivery system tailored for cancer treatment. This system integrates polymeric magnetic microparticles within a thermoresponsive hydrogel, enabling localized drug delivery. The hydrogel performs a multifaceted role: transports the microparticles, and controls the drug release rate, thereby prolonging treatment effectiveness. The production of microparticles composed of Gellan Gum and Alginate was optimized using a coaxial air-flow method. These microparticles were engineered to include superparamagnetic iron oxide nanoparticles and methylene blue as a model drug, which served the dual purpose of enabling magnetic hyperthermia and controlled drug release. Microparticles were embedded within thermoresponsive systems, particularly Pluronic gels (F127 and F68 in varying ratios) and a chitosan hydrogel with β-Glycerophosphate. Notably, a Pluronic gel ratio of 17:3 (F127:F68) with 2 and 5 w/w% of microparticles demonstrated the ability to instantaneously shift from a sol state, at room temperature, to a gel state at body temperature. On the other hand, the chitosan hydrogel with microparticles exhibited a more prolonged transition from to the gel state at 37°C while demonstrating non- cytotoxicity to Vero cell lines, more rigid structure than the Pluronic hydrogel, and was able retard the drug release from the microparticles. In conclusion, the designed microparticle/hydrogel systems showed potential as drug delivery systems for future cancer therapies. Their development represents a significant stride towards more targeted and less harmful cancer treatments, with promising applications in other diseases as well. |
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