Poly(beta-amino esters)
Poly(beta-amino esters) are cationic, hydrolytically degradable polymers that can
be produced as polymeric NPs for gene delivery. Green et al. [71] developed small
(~200 nm), positively charged (~10 mV), polymeric NPs by the self assembly of
poly(beta-amino esters) and DNA. These NPs had four times greater gene delivery
efficacy than those observed for Lipofectamine 2000 in human embryonic stem
(ES) cells. These materials exhibited minimal toxicity and did not adversely affect
the colony morphology or cause nonspecific differentiation of the ES cells.
Polylactide-co-Glycolide
PLGA is biodegradable, biocompatible and FDA-approved biomaterial that has
aroused considerable interest among researchers developing biodegradable NPs for
gene delivery. PLGA NPs complex with DNA at a low PLGA:DNA ratio and have
allowed robust gene expression in several cell types, including human MSCs [72].
They can be modified with other polymers such as PEI. Polyplexing with PEI
enhanced the cellular uptake of DNA complexed to PLGA NPs both in vitro and
in vivo [72, 73]. Park et al. [56] polyplexed four genes (SOX5, SOX6 and SOX9
genes fused to GFP, YFP or RFP marker genes) with PEI coated onto PLGA NPs
and obtained ~80% transfection efficiency in human MSCs.
Polyethylene-Glycol
PEG as such is not used as an NP. Repeating PEG moieties are usually added to
polymers to alter electrostatic binding properties and increase hydrophilicity of
NPs. The bulky nature of PEGylated polymers can also protect the NPs from
degradation by cellular enzymes, increase their stability and prevent aggregation.
PEGylation also enhances the transfection efficiency of NPs [74].
Chitosan and Chitosan Derivatives
Chitosan is a biodegradable, biocompatible, nontoxic, natural polysaccharide consisting
of repeating units of glucosamine and N-acetyl-glucosamine, the proportions of
which determine the degree of deacetylation and, hence, the polymer properties
including solubility, hydrophobicity and the ability to interact with polyanions.
Chitosan can bind to the minor groove of DNA to condense and protect it against
nuclease degradation without affecting the native conformation. Furthermore,
chitosan NPs are stable during storage and their preparation does not require
sonication and organic solvents, which minimizes possible damage to DNA during
complexation. Thus, it is a good candidate for non-viral gene delivery.
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P. Pushp et al.
Poly(beta-amino esters) are cationic, hydrolytically degradable polymers that can
be produced as polymeric NPs for gene delivery. Green et al. [71] developed small
(~200 nm), positively charged (~10 mV), polymeric NPs by the self assembly of
poly(beta-amino esters) and DNA. These NPs had four times greater gene delivery
efficacy than those observed for Lipofectamine 2000 in human embryonic stem
(ES) cells. These materials exhibited minimal toxicity and did not adversely affect
the colony morphology or cause nonspecific differentiation of the ES cells.
Polylactide-co-Glycolide
PLGA is biodegradable, biocompatible and FDA-approved biomaterial that has
aroused considerable interest among researchers developing biodegradable NPs for
gene delivery. PLGA NPs complex with DNA at a low PLGA:DNA ratio and have
allowed robust gene expression in several cell types, including human MSCs [72].
They can be modified with other polymers such as PEI. Polyplexing with PEI
enhanced the cellular uptake of DNA complexed to PLGA NPs both in vitro and
in vivo [72, 73]. Park et al. [56] polyplexed four genes (SOX5, SOX6 and SOX9
genes fused to GFP, YFP or RFP marker genes) with PEI coated onto PLGA NPs
and obtained ~80% transfection efficiency in human MSCs.
Polyethylene-Glycol
PEG as such is not used as an NP. Repeating PEG moieties are usually added to
polymers to alter electrostatic binding properties and increase hydrophilicity of
NPs. The bulky nature of PEGylated polymers can also protect the NPs from
degradation by cellular enzymes, increase their stability and prevent aggregation.
PEGylation also enhances the transfection efficiency of NPs [74].
Chitosan and Chitosan Derivatives
Chitosan is a biodegradable, biocompatible, nontoxic, natural polysaccharide consisting
of repeating units of glucosamine and N-acetyl-glucosamine, the proportions of
which determine the degree of deacetylation and, hence, the polymer properties
including solubility, hydrophobicity and the ability to interact with polyanions.
Chitosan can bind to the minor groove of DNA to condense and protect it against
nuclease degradation without affecting the native conformation. Furthermore,
chitosan NPs are stable during storage and their preparation does not require
sonication and organic solvents, which minimizes possible damage to DNA during
complexation. Thus, it is a good candidate for non-viral gene delivery.
62
P. Pushp et al.