Cationic Polymers

Polyplex (cationic polymer/DNA complex) formation is driven largely by electrostatic interactions of negatively charged DNA with cationic polymers, such as poly-L-lysine (PLL) [72,73], polyethylenimine (PEI) [74-77], poly(methacrylate) [78,79], poly(amidoamine) [80] and dendrimers [81-83], which serve to condense the DNA. Cationic polymers are capable of protecting DNA from degradation by nucleases [84], and the complexes enter cells either via adsorptive endocytosis [49,85] or by receptor-mediated endocytosis [86]. Cationic polymers have been used to deliver DNA to the lungs of animals and humans [59,87-98]. In a study including linear and branched PEIs, dendrimers, and a conjugate of Pluronic P123, Gebhart and Kabanov found that the difference in transfection efficiency could not be related to the structural differences of the cationic compound [99].

PEI/DNA polyplexes were found to maintain functional stability and provide 10-fold higher transfection efficiency in vivo than lipoplexes following nebulization [89]. Interestingly, PEI/DNA was more efficient in providing in vivo gene expression in the lungs compared to the nasal passageways [89]. Linear PEI (L-PEI) has achieved higher levels of transfection than 25 kDa molecular weight branched PEI following instillation in rats [96]. However, as with some viral and most synthetic systems, gene expression is typically transient [213]. Additionally, cationic polymers can be cytotoxic at high doses. Reviews of cationic polymer complexation with DNA can be found in Refs. 10, 75, and 101.

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