β-tcp modificado com pluronic® para liberação controlada de agentes aplicados na regeneração óssea em tratamento de osteoporose
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Data
2019-07-05
Autores
Ambrosio, Luísa Barrella
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Editor
Universidade Estadual Paulista (Unesp)
Resumo
A osteoporose é uma doença do tecido ósseo causada pela desregulação hormonal, que atinge uma grande parcela da população, principalmente mulheres pós-menopausa. Uma das principais consequências da osteoporose são fraturas, que ocorrem devido a diminuição da densidade óssea causada pela doença. Atualmente, busca-se uma maior eficácia em tratamentos, unificando a engenharia de tecidos e a liberação controlada de fármacos, em um sistema de drug delivery. Os compósitos são uma alternativa aos tratamentos atuais por unir em um só material as propriedades das cerâmicas e dos polímeros biodegradáveis, apresentando melhores características físicas, de biodegradabilidade e biocompatibilidade. A utilização de compósitos biocompatíveis e biodegradáveis na entrega de agentes osteogênicos, como fármacos, íons, proteínas ou sinalizadores celulares, tem se apresentado eficiente para utilização no tratamento de fraturas ósseas, com resultados positivos de osteoindução, osteintegração e reabsorção por parte do tecido, indicando o favorecimento da regeneração óssea. Desta maneira, a proposta deste trabalho foi o preparo de materiais compósitos cerâmico-polmérico para suporte de liberação controlada de agentes osteogênicos. Foram preparados compósitos de fosfato de cálcio na fase β e de copolímero Pluronic®, no qual incorporou-se íons cobalto, os fármacos alendronato ou o ranelato de estrôncio, para o estudo da liberação controlada destes agentes, visando o uso como enxerto ósseo no tratamento de osteoporose. Os agentes foram incorporados pelo método de dispersão sólida, e os materiais compósitos e a matriz polimérica foram caracterizados por difratometria de raios X, espectroscopia na região do infravermelho, calorimetria exploratória diferencial, análise termogravimética e microscopia eletrônica de varredura, possibilitando a identificação da composição e morfologia dos materiais. Os estudos de liberação foram realizados com êxito, aplicados na definição da melhor matriz polimérica para a liberação proposta, e a comparação e avaliação dos perfis de liberação de cada um dos agentes foi realizada. Os perfis de liberação dos compósitos β-TCP-Pluronic-Cobalto, β-TCP-Pluronic-Alendronato-1, β-TCP-Pluronic-Alendronato-2 e β-TCP-Pluronic-Ranelato-2, se mostraram adequados para a aplicação proposta, uma vez que as liberações ocorreram continuamente durante uma semana, período importante do processo da regeneração óssea.
Osteoporosis is a bone tissue disease caused by hormonal dysregulation, which affects a large portion of the population, especially postmenopausal women. Fractures are one of the main osteoporosis consequences, which occurs due the bone density decrease caused by the disease. Nowadays, more efficiently treatments are searched, combining tissue engineering and controlled drug release in a drug delivery system. Composite materials are an alternative in current treatment for finding in one single material the properties of ceramics and biodegradable polymers, presenting better physical characteristics, as biodegradability and biocompatibility. Biocompatible and biodegradable composite uses in the delivery of osteogenic agents, such as pharmaceuticals, ions, proteins or cell signaling, has been shown to be efficient in bone fracture treatment, with positive results of osteoinduction, osteointegration and tissue resorption, indicating the bone regeneration. In this way, this work proposed to prepare ceramic-polymer composite for support the osteogenic agents controlled delivery. It was prepared composites of calcium phosphate and copolymer Pluronic®, in which cobalt ions or the drugs alendronate or strontium ranelate were incorporated, for study the agents controlled release, aiming the uses as bone scaffold in osteoporosis treatment. The agents were incorporated by solid dispersion method, and the composites and polymer matrix were characterized by X-ray diffractometry, infrared spectroscopy, differential scanning calorimetry, thermogravimetric analysis and scanning electron microscopy, enabling composition and morphology identification of the material. The drug delivery studies were successfully performed, defining the best polymer for the proposed release, by comparation and evaluation of the agents release profiles. The release profiles of the composites β-TCP-Pluronic-Cobalt, β-TCP-Pluronic-Alendronate-1, β-TCP-Pluronic-Alendronate-2 and β-TCP-Pluronic-Ranelate-2, were shown to be appropriated in the proposed application, since the release occurred continuously during one week, an important period of the bone regeneration process.
Osteoporosis is a bone tissue disease caused by hormonal dysregulation, which affects a large portion of the population, especially postmenopausal women. Fractures are one of the main osteoporosis consequences, which occurs due the bone density decrease caused by the disease. Nowadays, more efficiently treatments are searched, combining tissue engineering and controlled drug release in a drug delivery system. Composite materials are an alternative in current treatment for finding in one single material the properties of ceramics and biodegradable polymers, presenting better physical characteristics, as biodegradability and biocompatibility. Biocompatible and biodegradable composite uses in the delivery of osteogenic agents, such as pharmaceuticals, ions, proteins or cell signaling, has been shown to be efficient in bone fracture treatment, with positive results of osteoinduction, osteointegration and tissue resorption, indicating the bone regeneration. In this way, this work proposed to prepare ceramic-polymer composite for support the osteogenic agents controlled delivery. It was prepared composites of calcium phosphate and copolymer Pluronic®, in which cobalt ions or the drugs alendronate or strontium ranelate were incorporated, for study the agents controlled release, aiming the uses as bone scaffold in osteoporosis treatment. The agents were incorporated by solid dispersion method, and the composites and polymer matrix were characterized by X-ray diffractometry, infrared spectroscopy, differential scanning calorimetry, thermogravimetric analysis and scanning electron microscopy, enabling composition and morphology identification of the material. The drug delivery studies were successfully performed, defining the best polymer for the proposed release, by comparation and evaluation of the agents release profiles. The release profiles of the composites β-TCP-Pluronic-Cobalt, β-TCP-Pluronic-Alendronate-1, β-TCP-Pluronic-Alendronate-2 and β-TCP-Pluronic-Ranelate-2, were shown to be appropriated in the proposed application, since the release occurred continuously during one week, an important period of the bone regeneration process.
Descrição
Palavras-chave
Osteoporose, Regeneração óssea, Tecnologia de liberação controlada, Materiais compostos, Osteogênese