Development of pH- and temperature-sensitive microgel particles: synthesis monitoring, characterisation and application as potential oral carriers.

Detalhes bibliográficos
Ano de defesa: 2019
Autor(a) principal: Souza, Esmar Faben
Orientador(a): Não Informado pela instituição
Banca de defesa: Não Informado pela instituição
Tipo de documento: Tese
Tipo de acesso: Acesso aberto
Idioma: eng
Instituição de defesa: Biblioteca Digitais de Teses e Dissertações da USP
Programa de Pós-Graduação: Não Informado pela instituição
Departamento: Não Informado pela instituição
País: Não Informado pela instituição
Palavras-chave em Português:
Link de acesso: http://www.teses.usp.br/teses/disponiveis/3/3137/tde-18072019-075603/
Resumo: Multi-sensitive microgel particles are covalently crosslinked polymeric chains with a colloidal dimension that can rapidly change their volume through various external stimuli such as pH, ionic strength, temperature, and magnetic and electric field. Due to these characteristics, increasing attention has been focus on the development of multi-sensitive microgels, mainly for application as drug delivery carriers. This study aimed to synthesise pH- and temperature-sensitive microgel particles, based on precipitation polymerisation of N-isopropylacrylamide and acrylic acid, with a defined size, narrow size distribution, spherical morphology and colloidal stability to be used as an oral drug carrier. In order to provide better biocompatibility and biodegradability in the synthesised material, some assays were performed, adding the chitosan biopolymer during the polymerisation of the monomers previously mentioned. This thesis also intended to contribute to a better understanding of the relationship between the microgel synthesis and their properties using spectroscopic techniques to monitor the microgel formation. A new approach was proposed to monitoring the process variables, monomer conversion and average particle size of the microgel particles, during precipitation polymerisation using NIR and UV-VIS-NIR high-resolution spectrophotometers coupled with a probe. Besides, the influence of reaction conditions in the physicochemical characteristics of microgel particles was extensively investigated as well as their potential as an oral drug carrier for insulin. The monitoring results pointed out the enormous potential of these spectroscopy techniques to monitor the precipitation polymerisation process, allowing control over the polymerisation reaction with quickly and directly acquisition of data in real-time. In general, pH- and temperature-sensitive microgels were successfully synthesised, and many formulations showed to be suitable for application as oral drug carriers. However, the preliminary in vitro release results were not satisfactory, and a more in-depth study between the interaction of the drug with the particles as well as the method of release is recommended. In conclusion, with a proper understanding of the influence of the process conditions (e.g., reagent concentrations) on the physicochemical properties of the microgels, it is possible to tailor the multi-sensitive microgels for the desired application.