Blood circulation time

The concept of de-PEGylation can be applied to the development of nanoparticle-based drug delivery systems. PEG is used for the modification of liposomes to increase their blood circulation time [38], However, it also prevents cellular uptake, resulting in a decrease in therapeutic efficiency thus, modifications of the liposome surface with PEG interfere with membrane fusion to the cell membrane and liposome decomposition [39]. One of the possible strategies to solve this problem is to cleave the PEG chains after the nanoparticle reaches the target site (Fig. 9). This system of de-PEGylation of liposomes is also useful in avoiding the immune... 

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... 

Liu et al. (2007) discovered that polyethylene glycol (PEG)ylated SWNTs are stable in vivo and demonstrate long blood circulation times and low uptake by the reticuloendothelial system. This group linked PEGylated SWNTs to an arginine-glycine-aspartic acid peptide, which was able to effectively target tumors in mice. 

Lipid moieties coupled to polyethylene glycol (PEG) have been used to increase the blood circulation time of lipoplexes (Fig. 32). The PEG-lipid conjugates such as DOPE-PEG, Chol-PEG, ceramides-PEG and their derivatives are then coformulated with the cationic lipid, helper lipid, and DNA. This results in coating the surface of the lipoplexes with PEG and preventing undesired association with plasma proteins or circulating cells (stealth liposomes). Recently, a-tocopheryl PEG-succinate (TPGS) was also used in gene delivery formulations because of its ability to confer not only a stealth property but also antioxidant and absorption enhancer properties [129]. 

A particular carrier system containing a cytotastic dmg is rapidly taken up by the MPS upon intravenous injection. How can one realistically extend the blood circulation time of this particulate carrier system keeping in mind that this system should be used in patients ... 

Hydrophilic-hydrophobic diblock copolymers exhibit amphiphilic behavior and form micelles with a core-shell architecture. These polymeric carriers have been used to solubilize hydrophobic drugs, to increase blood circulation time, to obtain favorable biodistribution, and to lower interactions with the reticuloen-... 

In general, the modification of particulate carriers using amphipathic polyethylene glycol (PEG)-containing molecules results in a prolongation of their blood circulation time [57,58], A phosphatidylethanolamine derivative with polyethylene glycol (PEG-PE) is widely used to increase the plasma retention of particulate carriers such as liposomes [59-61], polystyrene microspheres [62], and nanospheres... 

However, the degree of accumulation of liposomes in tumour tissue depends on their blood circulation time. In order to maximise the accumulation of liposomes, and thus boron, in the tumour, liposomes with long survival time in systemic circulation, should be employed. The liposomal circulation time may be dramatically increased by attachment of long flexible polyethylene glycol (PEG) chains to a proportion of the lipids in the liposomal membrane. Such sterically stabilised liposomes have been shown to circulate for several days, up to a week, without detection by the immune system. 

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. 

Thus, extension of the blood circulation time of the micelles as well as a regulated release rate of the CDDP from the micelle was concluded to be necessary to achieve a more effective anti-tumor activity. This was eventually achieved using PEG-PGlu instead of PEG-PAsp. Here, CDDP was loaded in the micelle in a similar manner to the PEG-PAsp metal complexation with the ligand substitution reaction between CDDP and the carboxylic group of PEG-PGlu (Fig. 3b) [60]. The formed micelle had a very narrow size distribution with an approximately 30 nm diameter. The PEG-PGlu(CDDP) micelle showed a more sustained release of CDDP (half-value period > 90 h) than... 

The typical blood circulation time for an eosinophil is approximately 6 hours, but it may survive weeks within tissues. Cytokines thought to be important in eosinophil production or function include lL-1, IL-3, GM-CSF, G-CSF, and perhaps most important, IL-5. Corticosteroids cause a transient margination of eosinophils and inhibit release of mature cells from the bone marrow." ... 

Puskas Z, Schuierer G (1996) Determination of blood circulation time for optimizing contrast medium administration in CT angiography. Radiologe 36(9) 750-757. 

As described in Sec. 2, polymeric micelles that are formed through either hydrophilic-hydrophobic interaction of PEG-based block copolymers or electrostatic interaction of PE G-polycation block copolymers with negatively charged macromolecules have attracted considerable attention in the field of drug delivery and gene delivery systems, owing to their excellent biocompatibility, long blood circulation time, and nontoxicity. In this section, the preparation and the characterization of end-functionalized polymeric micelles... 

Stealth micelles Have stabilizing PEG coronas to minimize opsonization of the micelles and maximize blood circulation times Clinical data have been reported on three stealth micelle systems SP1049C, NK911,and Genexol-PM 29... 

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