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Rheological analysis of thermoresponsive hydrogels with bioadhesive polymers for enhanced drug delivery
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Abstract(s)
Os sarcomas dos tecidos moles (STM) são tumores raros que surgem dos tecidos conjuntivos,
incluindo cartilagem, músculo, vasos sanguíneos, nervos e gordura. A cirurgia continua a ser
o tratamento primário, muitas vezes suplementada por quimioterapia e radioterapia.
Indicadores de mau prognóstico incluem tamanho grande do tumor, idade avançada, alto
grau, metástase ao diagnóstico, remoção incompleta, margens cirúrgicas positivas, invasão
profunda e necrose tumoral significativa. Abordar estes desafios requer uma estratégia de
tratamento abrangente. Recentemente, os hidrogeles termorresponsivos emergiram como
uma solução promissora para a administração localizada de medicamentos. Estes hidrogeles
transitam de líquido a gel à temperatura corporal, aumentando a retenção e a eficácia dos
agentes terapêuticos no local alvo. Ao incorporar propriedades bioadesivas, estes hidrogeles
garantem ação terapêutica prolongada com efeitos sistémicos mínimos, oferecendo uma
abordagem inovadora para melhorar os resultados do tratamento dos STM. Este projeto
explora o desenvolvimento de hidrogéis termorresponsivos para aplicação in situ nos STM.
Os principais aspetos investigados incluem o impacto das misturas de polímeros,
propriedades reológicas, otimização usando o design de experiências (DoE),
adesão/mucoadesão e testes de libertação in vitro. Os resultados destacam a eficácia do
polímero bioadesivo PVP na obtenção das propriedades reológicas desejadas e libertação
controlada de fármacos. As formulações de hidrogel contendo PVP exibiram propriedades
reológicas favoráveis, incluindo viscosidade controlada em diferentes taxas de cisalhamento
e temperaturas. Além disso, as formulações otimizadas demonstraram propriedades
mucoadesivas melhoradas, tornando-as particularmente adequadas para aplicações de
administração direcionada de fármacos. O hidrogel otimizado P407/P188/PVP exibiu
propriedades viscoelásticas e físico-químicas adequadas para eficácia pré-clínica, com
potenciais aplicações em sistemas de administração de medicamentos.
As direções futuras de pesquisa incluem a realização de estudos in vivo para avaliar a
biocompatibilidade, segurança e eficácia terapêutica do hidrogel. Adicionalmente, explorar a
integração de outros agentes bioativos e polímeros pode expandir a aplicabilidade do hidrogel
e aumentar seus benefícios terapêuticos. Esta pesquisa contribui significativamente para o
avanço na administração direcionada de fármacos, demonstrando o potencial dos hidrogeles
termorresponsivos para revolucionar o tratamento de doenças localizadas, particularmente
em oncologia, onde a administração direcionada e sustentada é crítica.
Soft tissue sarcomas (STS) are rare tumors arising from connective tissues, including cartilage, muscle, blood vessels, nerves, and fat. Surgery remains the primary treatment, often supplemented by chemotherapy and radiotherapy. Poor prognosis indicators include large tumor size, advanced age, high grade, metastasis at diagnosis, incomplete removal, positive surgical margins, deep invasion, and significant tumor necrosis. Addressing these challenges requires a comprehensive treatment strategy. Recently, thermoresponsive hydrogels have emerged as a promising solution for localized drug delivery. These hydrogels transition from liquid to gel at body temperature, enhancing the retention and effectiveness of therapeutic agents at the target site. Incorporating bioadhesive properties, these hydrogels ensure prolonged therapeutic action with minimal systemic side effects, offering an innovative approach to improve STS treatment outcomes. This project explores the development of thermoresponsive hydrogels for in situ application in STS. Key aspects investigated include the impact of polymer mixtures, rheological properties, optimization using design of experiments (DoE), adhesion/mucoadhesion, and in vitro release tests. The findings highlight the effectiveness of the bioadhesive polymer PVP in achieving desired rheological properties and controlled drug release. Hydrogel formulations containing PVP exhibited favorable rheological properties, including controlled viscosity across different shear rates and temperatures. Additionally, the optimized formulations demonstrated enhanced mucoadhesive properties, making them particularly suitable candidates for targeted drug delivery applications. The optimized P407/P188/PVP hydrogel exhibited suitable viscoelastic and physicochemical properties for preclinical efficacy, with potential applications in drug delivery systems. Future research directions include conducting in vivo studies to assess the hydrogel´s biocompatibility, safety, and therapeutic efficacy. Additionally, exploring the integration of other bioactive agents and polymers could expand the hydrogel´s applicability and enhance its therapeutic benefits. This research contributes significantly to the field of advanced drug delivery systems, demonstrating the potential of thermoresponsive hydrogels to revolutionize the treatment of localized diseases, particularly in oncology where targeted and sustained delivery is critical.
Soft tissue sarcomas (STS) are rare tumors arising from connective tissues, including cartilage, muscle, blood vessels, nerves, and fat. Surgery remains the primary treatment, often supplemented by chemotherapy and radiotherapy. Poor prognosis indicators include large tumor size, advanced age, high grade, metastasis at diagnosis, incomplete removal, positive surgical margins, deep invasion, and significant tumor necrosis. Addressing these challenges requires a comprehensive treatment strategy. Recently, thermoresponsive hydrogels have emerged as a promising solution for localized drug delivery. These hydrogels transition from liquid to gel at body temperature, enhancing the retention and effectiveness of therapeutic agents at the target site. Incorporating bioadhesive properties, these hydrogels ensure prolonged therapeutic action with minimal systemic side effects, offering an innovative approach to improve STS treatment outcomes. This project explores the development of thermoresponsive hydrogels for in situ application in STS. Key aspects investigated include the impact of polymer mixtures, rheological properties, optimization using design of experiments (DoE), adhesion/mucoadhesion, and in vitro release tests. The findings highlight the effectiveness of the bioadhesive polymer PVP in achieving desired rheological properties and controlled drug release. Hydrogel formulations containing PVP exhibited favorable rheological properties, including controlled viscosity across different shear rates and temperatures. Additionally, the optimized formulations demonstrated enhanced mucoadhesive properties, making them particularly suitable candidates for targeted drug delivery applications. The optimized P407/P188/PVP hydrogel exhibited suitable viscoelastic and physicochemical properties for preclinical efficacy, with potential applications in drug delivery systems. Future research directions include conducting in vivo studies to assess the hydrogel´s biocompatibility, safety, and therapeutic efficacy. Additionally, exploring the integration of other bioactive agents and polymers could expand the hydrogel´s applicability and enhance its therapeutic benefits. This research contributes significantly to the field of advanced drug delivery systems, demonstrating the potential of thermoresponsive hydrogels to revolutionize the treatment of localized diseases, particularly in oncology where targeted and sustained delivery is critical.
Description
Trabalho Final de Mestrado Integrado, Ciências Farmacêuticas, 2024, Universidade de Lisboa, Faculdade de Farmácia.
Keywords
Thermoresponsive hydrogel Rheological characterization Design of experiments (DoE) Controlled drug delivery Mestrado Integrado - 2024