Ovarian cancer is one of the five most common causes of cancer death in women in the USA and UK. It is usually diagnosed when it is well established beyond the ovary in the peritoneum. Intravenous injection of cisplatin is a common palliative therapy for ovarian cancer patients. Intraperitoneal therapy has been shown to improve survival for patients. Poly(lactide-co-glycolide) (PLGA) is a biodegradable polyester which has been proven safe for medical implantation. PLGA microspheres or fibres have been considered in this work as depots for delivering intraperitoneal cisplatin directly to the tumour site. The aims of this work were (1) to develop microsphere depot formulations with improved drug release profiles compared to previous work; (2) Novel cisplatin containing solid and hollow fibres were to be developed and investigated as alternative structures for depot devices; (3) The drug release profiles were to be examined using mathematical models to allow rational comparison of the devices. It was found that cisplatin containing PLGA 65:35 solid and hollow fibres represent a novel, reproducible formulation for encapsulating higher amounts of cisplatin for an equivalent mass of excipient than other polymer formulations. The fibres developed in this study were able to maintain elevated concentrations of unbound cisplatin in the presence of a biological matrix for approximately 100 hours in vitro.

Orientador: Laercio Luis Vendite / Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Matematica, Estatistica e Ciencia da Computação / Made available in DSpace on 2018-08-09T23:40:27Z (GMT). No. of bitstreams: 1 Alonso_AnaCamilaRodrigues_M.pdf: 1099108 bytes, checksum: f7bd5d3bc8e683d7332a70d7a75c8405 (MD5) Previous issue date: 2007 / Resumo: O câncer de ovário é a neoplasia mais letal do aparelho genital feminino. É necessário fazer um estabelecimento precoce de seu diagnóstico e uma correta abordagem terapêutica para interferir na sua história natural. Com a intenção de melhorar a metodologia para distinguir benignidade de malignidade dos tumores de ovário foram estudadas associações de métodos. Jacobs et al. foram os primeiros autores a idealizar um índice de risco de malignidade (IRM) para tumores de ovário, incorporando estado menopausal, achados ultra-sonográficos e o nível sérico do CA 125. Neste trabalho, um modelo matemático é elaborado para auxiliar no diagnóstico diferencial de benignidade e malignidade dos tumores ovarianos clinicamente restritos aos ovários. A ferramenta utilizada para desenvolver o modelo é a teoria dos conjuntos, por sua capacidade em lidar com incertezas. Inicialmente, as variáveis de entrada - Estado Menopausal, Achados ultrasonográficos e Nível de CA 125 - e a variável de saída do sistema - Tipo de Tumor ¿ foram consideradas como variáveis lingüísticas e seus valores como conjuntos fuzzy. O modelo construído é mais abrangente que o índice de risco de malignidade proposto por Torres et al., pois no modelo temos que o estado menopausal e os achados ultra-sonográficos são considerados como variáveis contínuas. A saída dos sistema, também contínua, propicia uma transição gradual entre tumor benigno e maligno, o que é mais coerente com a realidade / Abstract: The ovarian cancer is the most lethal neoplasy of the femine genital system. It is necessary to do a precocious establishment of its diagnosis and a correct therapeutical approach to intervene in the natural history. With the intention to improve the methodology to distinguish benignancy from malignancy of the ovarian tumors methods¿s associations had been studied. Jacobs et al. were the first authors to idealize the risk of malignance index for ovarian tumors, incorporating menopausal status, ultrasound findings and the serum level CA 125. In this work, a mathematical model is elaborated to auxiliary in the diferential diagnosis of the benignancy clinically restricted to the ovaries. The tool used to developed the model is the fuzzy sets theory for capacity in dealing with uncertainties. Inicially, input variables - menopausal status, ultrasound findings and CA 125 level ¿ and the system output variables - tumor¿s type - they had been considered with linguistics variables and its values with fuzzy sets. The constructed model is more comprehensive than risk of malignancy index propose to Torres et al., therefore the menopausal status and the ultrasound findings are considered as a continuous variable. The system output, also continuous, give a gradual transition between benign and malignant tumor, what is more coherent with the reality / Mestrado / Biomatematica / Mestre em Matemática Aplicada