Nanocarriers, circulation

Due to its hydrophilic nature, dextrans have also been used to conjugate bioactive substances (e.g., dmgs, enzymes, hormones, and antibodies) to prolong circulation lifetimes, increase stability in vivo, or depress antigenicity. For example, dextran nanoparticles have been conjugated with insulin for oral delivery. These nanocarriers can protect insulin from degradation in the gut and modulate release profiles. ... 

In spite of all the advantages, cationic nanoparticles have some challenges. Some major drawbacks of these systems include instability, risk of aggregation, toxicity, opsonization and clearance by the mononuclear phagocyte system (MPS). To overcome these problems, cationic nanoparticles should be as small and neutral as possible and nanoparticles can be coated with PEG. PEG can provide a hydrophilic surface to nanocarriers and also a cationic surface charge and prevent opsonization. In this way, PEG-coated nanoparticles have a prolonged circulation life and protect photolytic degradation. 

To solve these challenges, PEI is conjugated with hydrophilic polymers like PEG. Nanocarriers produced from PEG-PEI copolymers also have a longer circulation time since PEG conjugation prevents opsonization. PEG-PEI (800 kDa) polyplexes were manufactured through grafting of transferrin to PEG and this modification resulted in a five-fold increase in transfection efficiency and decreased toxicity. ... 

Proteins as biomolecules are always liable to enzymatic degradation and digestion as well as to changes in pH and temperature. On the other hand, the use of protein nanocarriers to entrap dmg molecules will help evade its uptake by the immune system, prevent opsonization and its subsequent phagocytosis to a great extent, improve circulation of the dmg by renal and hepatic re-absorption, and much more. Several techniques have been proposed in the literature to prevent the acid or enzymatic degradation of protein nanocarriers [62, 93, 105, 106]. 

In addition to surface modification, particle size is another key factor that affects the circulation time of nanocarriers. The smaller the particle size, the lesser will be the protein adsorption and slower the clearance. To demonstrate... 

A combinatorial coating of PEG and cationic WSC, on PLA nanoparticles, has yielded greatly prolonged circulation time for the nanocarriers in vivo. In contrast to PLA nanoparticles treated with PEG or WSC alone, PEG and WSC synergisticaUy provided a strong inhibition of macrophage uptake and extended the circulation half-life up to 63.5 h, with concomitant reduced liver sequestration. This ty2 value was much longer than that of control PEG/PVA nanoparticles (1.1 h) as well as that of PLA nanoparticles stabilized with PEG/CPCTS (anionic N-carboxy propionyl... 

A serious limitation with all pharmaceutical nanocarriers, including liposomes, is that the body normally treats them as foreign particles, and thus, they become easily opsonized and removed from the circulation long prior to completion of their function. 

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