Charge nanocarriers

Drug loading in the polymeric nanocarriers is generally achieved by a method requiring the use of organic solvent to dissolve the drug, dialysis, oU-in-water emulsion solvent evaporation, and solid dispersion. Dmg incorporation can modify various physicochemical parameters of the carrier like size or surface charge. 

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. 

On the other hand, PEI nanocarriers have some toxicity problems. They are reported to show two types of toxicity one of them is immediate toxicity due to free PEI. Free PEI interacts with serum proteins which have a negative charge and also erythrocytes. This interaction results in precipitation in huge clusters, adherence to the cell membrane and damage to the plasma membrane. The other type is delayed toxicity as a consequence of cellular processing of the PEI polyplexes. Another toxicity problem also arises from the linear structure of PEI. When PEI polyplexes were administered via the intravenous route to mice, lethal side effects were observed. On the other hand, linear PEIs have higher transfection efficiency and lower cytotoxicity than branched PEIs, according to several studies. ... 

Nanocarriers which have an anionic or neutral surface charge can be also be coated with PLL to render a cationic surface charge. " ... 

Micelles are formed by copolymers auto-assembly of amphiphilic or oppositely charged properties in a liquid. They are sized between 20-100 nm and are described as core-shell spherieal nanocarriers. Generally they are obtained from two different parts, core and corona or shell. The hydrophilic part of the copolymer constitutes the brush-like corona and the hydrophobic part constitutes the core in water. The core is generally designed as the encapsulation area for hydrophobic dmgs (see Figure 11.6). 

Besides high thermodynamic stability and drug encapsulation efficiency, the cellular uptake and tissue penetration of LDBC micelles for drug delivery can be tuned by surface functionalization with targeting agents and changes in surface charge. For instance, a dendron-based nanocarrier platform was developed based... 

In this chapter, the design of stmcturally defined dendritic and protein-based polyelectrolyte nanocarriers is presented and the impact of their macromolecular architectures and the presence of multiple charges and charge densities on cellular uptake, trafficking, and cell toxicity is discussed. 

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