Submitted by MATHEUS TEIXEIRA SEIXAS E SILVA null (matheus.seixas88@gmail.com) on 2018-03-28T11:31:25Z No. of bitstreams: 1 Dissertação_Matheus_Teixeira_Seixas_e_Silva.pdf: 1385952 bytes, checksum: 8a9088d80a7f169efa4152e160a01d47 (MD5) / Approved for entry into archive by Alexandra Maria Donadon Lusser Segali null (alexmar@fcav.unesp.br) on 2018-03-28T13:19:40Z (GMT) No. of bitstreams: 1 silva_mts_me_jabo.pdf: 1385952 bytes, checksum: 8a9088d80a7f169efa4152e160a01d47 (MD5) / Made available in DSpace on 2018-03-28T13:19:40Z (GMT). No. of bitstreams: 1 silva_mts_me_jabo.pdf: 1385952 bytes, checksum: 8a9088d80a7f169efa4152e160a01d47 (MD5) Previous issue date: 2018-03-09 / Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) / As falhas ósseas, principalmente as críticas, representam entidade à parte. Para que se possa gerar reconstituição de falhas ósseas críticas é necessário o auxílio de métodos de enxertia que promovam osteoindução e osteocondução. É frequente a busca de substitutos ósseos de forma a aprimorar técnicas já existentes que promovam osteogênese visando o rápido restabelecimento de suas funções. O enxerto autógeno isolado pode ser insuficiente nas falhas ósseas críticas apesar de ser a melhor opção, causa maior morbidade na recuperação do paciente. O omento tem sido frequentemente estudado na cirurgia devido suas diversas propriedades vasculares vantajosas em locais pouco vascularizados, melhorando a cicatrização e controle de infecção. Este estudo teve como objetivo avaliar a capacidade angiogênica e osteoindutora de fragmentos ósseos xenógenos autoclavados implantados, com ou sem a presença de omento no espaço subcutâneo (S1), espaço subcutâneo juntamente com o omento (S2) e região intraóssea (S3) em coelhos. Utilizou-se 30 animais em um único grupo onde cada animal recebeu os fragmentos ósseos em três sítios corpóreos diferentes (S1, S2 e S3) e foram avaliados por métodos histológicos sua atividade angiogênica e osteogênica. Diante dos resultados obtidos foi possível observar que, o material implantado foi rejeitado devido à reação de corpo estranho ter sido intensa e persistente por todos os tempos (7, 15, 30, 45, 60 dias) de avaliação em todos os locais de implantação. Não houve osteogênese em nenhum dos locais de implantação. Foi possível comparar a angiogênese entre locais de implantação avaliando a infiltração vascular no interior dos fragmentos ósseos, onde S2 apresentou melhores resultados, com início de infiltração vascular aos 7 dias, enquanto que os demais grupos se iniciaram aos 30 dias. Conclui-se com este estudo que diante desta metodologia de preparo de implante ósseo xenógeno, provavelmente não houve remoção completa da antigenicidade, nem mesmo a preservação das BMPs, mas foi possível afirmar que o contato com o omento foi capaz de aumentar a angiogênese nos fragmentos implantados em comparação com os demais locais. / Bone failures, especially criticism, represent a separate entity. In order to generate reconstitution of critical bone defects it is necessary to use grafting methods that promote osteoinduction and osteoconduction. The search for bone substitutes is frequent in order to improve existing grafting techniques for the rapid restoration of their functions. The isolated autogenous graft may be insufficient in the critical bone faults although it is the best option, it causes greater morbidity in the recovery of the patient. The omentum has frequently been studied in the surgery due to its several advantageous vascular properties in places little vascularized, improving the cicatrization and control of infection. The purpose of this study was to evaluate the angiogenic and osteoinductive capacity of implanted autogenous xenogene bone fragments, with or without the presence of omentum in the subcutaneous space (S1), subcutaneous space together with the omentum (S2) and intraosseous region (S3). Thirty animals were used in a single group where each animal received the bone fragments at three different body sites (S1, S2 and S3) and their angiogenic and osteogenic activity were assessed by histological methods. In view of the results obtained, it was possible to observe that the implanted material was rejected because the foreign body reaction was intense and persistent at all times (7, 15, 30, 45, 60 days) of evaluation at all implantation sites. There was no osteogenesis at any of the implantation sites. It was possible to compare the angiogenesis between implantation sites by evaluating the vascular infiltration within the bone fragments, where S2 presented better results, with vascular infiltration beginning at 7 days, while the other groups started at 30 days. It was concluded from this study that in view of this xenogen graft preparation methodology, there was probably no complete removal of the antigenicity, not even the preservation of the BMPs, but it was possible to affirm that the contact with the omentum was able to increase the angiogenesis in the fragments in comparison with the other sites. / 148731/2016-3

Localized drug delivery is emerging as an effective technique due to its ability to administer therapeutic concentrations and controlled release of drugs to cancer sites in the body. It also prevents the contact of harsh chemotherapy drugs to healthy regions in the body that otherwise would become exposed to current treatments. This study reports on a model chemotherapy drug delivery system comprising non-ionic surfactant vesicles (niosomes) packaged within a temperature-sensitive chitosan network. This smart packaging, or package-within-a package system, provides two distinct advantages. First, the gel prevents circulation of the niosomes and maintains delivery in the vicinity of a tumor. Secondly, the chitosan network protects the niosomes against fluctuations in tonicity, which affects delivery rates. Tonicity is the sum of the concentrations of the solutes which have the capacity to exert an osmotic force across the membrane. Release rates were monitored from both bare niosomes alone and niosome-embedded, chitosan networks. It was observed that chitosan networks prolonged delivery from 100 hours to 55 days in low ionic strength environment and pH conditions similar to a tumor site. The primary effect of chitosan is to add control on release time and dosage, and stabilize the niosomes through a high ionic strength surrounding that prevents uncontrolled bursting of the niosomes. Secondary factors include cross-link density of the chitosan network, molecular weight of the individual chitosan polymers, dye concentration within the niosomes, and the number density of niosomes packaged within the chitosan network. Each of these factors can be altered to fine-tune release rates. Release rate experiments were conducted with 5,6-carboxyfluorescein, a fluorescent dye and chemotherapeutics paclitaxel and carboplatin. In vitro studies showed a preferential affinity of the smart packaged system to ovarian carcinoma cell line OV2008 as compared to normal epithelial cell lines of Ilow and MCC3. Further, feasibility of the drug delivery system was evaluated in vivo. Toxicity studies revealed that the system was non-toxic and feasible in vivo. The final outcome of this study includes tuning of the variables mentioned above that will contribute to the development of low cost and improved methods for drug delivery with application to intracavitary ovarian cancer treatment and other types of cancer