Cationic Polymers for the Delivery of Therapeutic Nucleotides - Nanotechnology for the Delivery of Therapeutic Nucleic Acids - page 41

conjugates formed stable complexes with DNA, only the dextran-
spermine (D-SPM) polycations of defined MW are found to be
active in transfecting a wide range of cell lines attributed

to spermine residues, which play a crucial role in cell transfection.
The complexes formed between D-SPM and pDNA exhibit a
hydrophilic surface due to the saccharides building units of the
polymer backbone. Such hydrophilic nature limits the cell uptake
of the complexes. Azzam

in vitro

reported higher spermine ratios of
grafted oligoamines resulted in high gene expression, whereas
low to negligible expressions were obtained with lower spermine
contents.

et al.

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Further, hydrophobization of D-SPM was achieved by
treating the polymer with N-hydroxysuccinimide derivatives of
cholesterol and fatty acids. The oleate-modified D-SPM remarkably
enhanced the gene expression in contrast to unmodified D-SPM,
which resulted with a drastic decrease in the transfection yields.
Modified D-SPM derivatives of other fatty acids and cholesterol
showed improved transfection yields in comparison to unmodified
D-SPM. This improvement in cell transfection was attributed to
oleate residues that probably play a role in increasing stability and
uptake of polycation-DNA complexes

. Similarly, Hosseinkhani et al.

reported modification of the D-SPM polycation with PEG resulted
in high transfection yield in serum-rich medium. This offers a new
biodegradable polycation based on natural components, which is
capable of transfecting cells and tissues

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in vitro and in vivo .

2.3.4 Dendrimers

Dendrimers are spherical, highly branched, three-dimensional
polymers having ability to interact with various forms of nucleic
acids such as pDNA, antisense oligonucleotides, and RNA. The
interaction between the dendrimer and the nucleic acids is purely
electrostatic where the cationic dendrimer condenses the anionic
nucleic acids. The nature of the dendrimer nucleic acid complex
depends on various factors like stoichiometry, concentration of
dendrimer-amines and nucleic acid-phosphates, as well as bulk
solvent properties like pH, salt concentration, etc. The net positive
charge of the dendrimer nucleic acid complex determines the
transfection efficiency. Dendrimer helps in DNA condensation
and endosome release due to the presence of cationic amino acid