Particle blood circulation time

Approaches to Increase Particle Blood Circulation Time... 

PEG is hydrophilic and is widely used in biological research because it protects surfaces from interacting with cells or proteins. Thus, coated particles may result in increased blood circulation time. For their preparation, 10-mg magnetite particles were dispersed in 1.0 mU of deoxygenated water by sonication for 30 min. The aqueous dispersion of MNPs was dissolved in the aqueous cores of reverse micelles... 

In addition to PEGylation, polyvinyl pyrolidone (PVP) nanoparticles modified with hydrophilic polaxa-mine have been reported to adsorb less protein than the unmodified particles, conventional liposomes, and stealth liposomes.Polystyrene microspheres coated with lecithin and particles coated with Pluronic were also observed to adsorb less protein and demonstrate a prolonged blood circulation time without adversely affecting the safety profile of the drug. 

Surface modification by polymer adsorption is an alternative to surface modification by polymer grafting. For example, polystyrene nanospheres coated by Poloxamer or Poloxamine (Ilium and Davis, 1983 Muller, 1991) or poly(methyl methacrylate) colloidal carriers coated by Poloxamer (Trds-ter and Kreuter, 1988) circulate longer in blood. This family of surfactants consist of poly(propylene glycol) (PPG) blocks, which adsorb on the hydrophobic polystyrene surface, and of more hydrophilic PEG blocks, which stick out of the surface in aqueous solutions and prevent opsonin adsorption. In spite of the increase in blood circulation time, particle coating by polymer adsorption was found to have several drawbacks (Petrak, 1993) ... 

Figure 7 shows that blood circulation time after i.v. administration in mice increases as the molecular weight of PEG increases, presumably due to an increase in the protective effect of the coating PEG layer. Five minutes after injection, 66% of noncoated particles were accumulated in the liver. 

Both intact carotenoids and their apolar metabolites (retinyl esters) are secreted into the lymphatic system associated with CMs. In the blood circulation, CM particles undergo lipolysis, catalyzed by a lipoprotein lipase, resulting in the formation of CM remnants that are quickly taken up by the liver. In the liver, the remnant-associated carotenoid can be either (1) metabolized into vitamin A and other metabolites, (2) stored, (3) secreted with the bile, or (4) repackaged and released with VLDL particles. In the bloodstream, VLDLs are transformed to LDLs, and then HDLs by delipidation and the carotenoids associated with the lipoprotein particles are finally distributed to extrahepatic tissues (Figure 3.2.2). Time-course studies focusing on carotenoid appearances in different lipoprotein fractions after ingestion showed that CM carotenoid levels peak early (4 to 8 hr) whereas LDL and HDL carotenoid levels reach peaks later (16 to 24 hr). 

As described above, the circulation time of a particulate carrier in the blood can be prolonged using stealth technology to enhance particle hydrophilicity. If the circulation time is sufficiently prolonged and the particle size does not exceed, say, 0.2 urn, then accumulation at tumor and inflammation sites (EPR-effect) can be observed. 

Figure 24 illustrates possible flocculation and chaining of particles in flow conditions. Larger particles close to the walls of the vessels experience greater shearing forces because of the nature of the flow patterns shown. Particles that adhere to er5dhrocytes move with them until detachment, often prolonging their own circulation times. Adhesion, seen as a prerequisite to cellular uptake from blood and interstitial fluids is not a foregone conclusion. The probability of adhesion, Padheaon can be written phenomenologically as in Figure 24. The factors include particle diameter, flow rate, the density of receptors, and the force of attraction between particle and receptor.

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