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Conception, Preparation & Characterization of nanoparticles of complex shapes : Study of their in vivo fate

Abstract : The drug targeting strategy aims not only to reduce the amount of administered drugs, but also to improve the benefit/risk ratio for the patient. Specific cellular delivery is raised while toxic effects caused by non specific delivery are weakened.To be fully efficient various vectors have been proposed, which are not only able to encapsulate the therapeutic molecules, but are also meant to interact efficiently with target cells. From this point of view, polymer nanoparticles are interesting objects for specifically targeting cells because of a unique combination of a nanometric size and the possibility to considerably modulate their physico-chemical properties.To this day the influence of the morphology of micro- and nanoparticles on their biodistribution is mostly unknown. However only a few studies suggest that the shapeof objects introduced in the body has a major influence on their fate in fluids[1], in vitro [2], and in vivo. Thus the observation of micro-organisms shows that shape not only influences their displacement, but also their capacity to interact with cells and the capture by macrophages.Understanding, at the micro- and nanometric levels the influence of shape on the interaction between particles and cells presents an undeniable scientific andpharmaceutical interest. Within this framework, the objective of our project is toidentify the different mechanisms or phenomena that the shape might impact, and to try to quantify their significance. More and more studies on the fabrication of micro and nanoparticles are emerging, but almost no data referred to the influence of shape on the behavior of these objects.To realize this study, we focused on producing non spherical particles of controlledshape and surface, either by auto-assembly of copolymers of poly(gamma-benzyl-Lglutamate)or by deformation of spherical nanoparticles. Then we studied the influence of shape on the in vitro interactions with characterized surfaces throughsurface plasmon resonance, on the interactions with cells (Human umbilical veinendothelial cells, HUVEC), and on the in vivo fate of the particles. All these elements demonstrated that the morphology of micro- and nanoparticles must be considered as a major factor to modulate their in vivo fate.
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Olivier Cauchois. Conception, Preparation & Characterization of nanoparticles of complex shapes : Study of their in vivo fate. Human health and pathology. Université Paris Sud - Paris XI, 2011. English. ⟨NNT : 2011PA114841⟩. ⟨tel-00659379⟩

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