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Development of polymer-based delivery systems for the delivery of fusogenic factors
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Resumo(s)
Ischemic stroke ranks among the leading cause of death and adult disability in
developed countries. An ischemic event leads to the formation of an area- called
penumbra – that despite the higher risk of permanent damage can be recovered with
adequate therapy. Therefore it is critical to develop therapeutic approaches aimed at
regenerating the ischemic brain. Due to the short time window for therapy and the
complications associated with the administration of large and frequent doses of
therapeutic molecules, it is vital to develop delivery systems with controlled release.
Our aim is to develop such a system for delivery of therapeutic molecules to the
stroke area, in order to enhance the recovery of the damaged brain. For this purpose,
Poly-lactic Acid (PLA) nanoparticles and Alginate/Chitosan nanoparticles, with a mean
diameter of 290 nm, were prepared by a multiple emulsion technique and by ionotropic
pre-gelation of alginate/chitosan polyelectrolyte complexation, respectively. When
BSA was used as a model protein, its release from Alginate/Chitosan nanoparticles
showed a burst release in the first hours, with 80% of entrapped BSA released by day
three. This result shows that these systems are adequate for treatment of an ischemic
episode, where it is critical to deliver an initial burst of therapeutic agent followed by a
steady, slow release over time.
Both types of nanoparticles presented no in vitro toxicity on the tested cell lines
and in vivo analysis of nanoparticles loaded with Rhodamine 6G injected into the
subretinal space of C57Bl6 mice showed no macroscopic signs of inflammation.
Finally, the biodistribution of nanoparticles administered intravenously in CD1 and
nude mice suggest that the nanoparticles can travel along the bloodstream of the
experimental animals and accumulate in particular tissues.
These results show that the developed systems can be part of a successful approach to
treat ischemic events, by delivering therapeutic molecules and releasing them with an
adequate profile.
Descrição
Disertação de mest., Ciências Biomédicas, Departamento de Ciências Biomédicas e Medicina, Univ. do Algarve, 2011
Palavras-chave
Ciências biomédicas AVC Acidente vascular cerebral Terapias Transplante de medula