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Colagénio da Catostylus tagi como matriz polimérica destinada à veiculação de fármacos proteicos
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Resumo(s)
Despite the great potential of protein pharmaceuticals in the pharmaceutical industry, proteins are rather fragile molecules and their administration often requires encapsulation in protective systems. In this work, a microparticulate protein delivery system was developed using collagen from the medusa Catostylus tagi as polymeric matrix. Collagen microparticles (CMPs) were produced by an emulsification-gelationsolvent extraction method, and a high loading efficiency was found for the entrapment of two model proteins – lysozyme and α-lactalbumin. A fraction of CMPs was separated and chemically treated with genipin (GP) and another with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC), in order to strengthen the collagenous matrix and reduce pore size. The non-crosslinked CMPs were spherical, rough-surfaced and had an average size of 5-15 μm. Slight size decrease, along with the reduction in pore size and number was found to occur upon treatment with EDC. When the particles were treated with GP, in contrast, no reticulation could be measured under the conditions used, and the particles suffered shape modification and diameter enlargement. These results pointed out to the unsuitability of GP as a crosslinking agent for this purpose and its use was hence abandoned.
The EDC-crosslinked microparticles showed a moderate hydrophobic behavior. A positive surface charge was assessed by zeta potential determination, which suggested a higher affinity towards negatively charged molecules and cellular membranes.Untreated collagen matrixes, due to their weakness and large pore size, seemed unable of significantly retaining entrapped molecules; chemical treatment with EDC, on the other hand, produced microparticles that were significantly resistant to water uptake, allowing a slow and sustained release of the proteins, as shown by in vitro experiments.
Finally, the assessment of lysozyme’s biological activity showed that the protein remained active after both the encapsulation and reticulation processes.
In summary, the work here described shows the potential use of a marine collagen in the production of microparticles for the controlled release of therapeutic proteins.
Descrição
Tese de mestrado, Farmacotecnia Avançada, Universidade de Lisboa, 2009
Palavras-chave
Teses de Mestrado Farmacotecnia Tecnologia farmacêutica