Cellular Uptake of pSi Particles

As stated previously, pSi particles are targets for internalization by cells of the mononuclear phagocyte system, and stealthing with PEG delays their uptake. For third-generation delivery systems, the first level of targeting for intravascularly administered particulates is the vascular endothehum. In vitro, vascular endothelial cells are able to internalize micron-sized pSi particles by phagocytosis and macropinocytosis (R.E. Serda et al, unpublished results). This is more compHcated in vivo, where serum opsonization coats the microparticles and alters their ability to adhere to the vascular wall. In this section we describe cellular uptake of pSi nanoparticles and microparticles, and examine the characteristics of pSi microparticles which alter this phenomenon. 

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The size polydispersion, and the very small yield in the micron size range suitable for drug delivery applications, constitutes a significant drawback of this technique. Size uniformity is important for shared biodegradation rates, which depend on both size and porosity. Another drawback of this technique is the shape polydispersion, which affects both the cellular uptake of pSi particles and blood flow characteristics [24]. Microparticle uptake by the reticuloendothelial system (RES), as well as margination and adhesion dynamics in the bloodstream, are strongly correlated to both the shape and size of the particles [21, 25, 26). 

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