Biomedical Engineering Reference
In-Depth Information
Similar to liposomes, cationic polymers may also be used
to condense negatively charged nucleic acids via electrostatic
interactions. The flexibility of polymers in constructing a broad
range of nanostructures such as polyplexes, polymeric micelles,
and dendrimers makes polymers suitable to develop as non-viral
carriers. Since polymers can be extensively and precisely engineered
due to their exclusive physicochemical properties, research
efforts have been devoted to improving polymers with greater
biocompatibility, stability in biological systems, and intracellular
trafficking.
1
Among several different types of carriers, including both
synthetic and biological polymers, biological polymers are found to
have a higher biocompatibility and a relatively low toxicity. Two
naturally formed molecules, chitosan and poly(amine-cyclodextrin),
may be representative of biological polymers. Both materials have
been widely used for nucleic acid delivery mainly because of their
cationic charge, excellent biocompatibility, and biodegradable
characteristics. However, chitosan has minimal solubility and a low
buffering capacity at physiological pH, resulting in significantly
reduced transfection efficiency compared to other cationic polymers
such as polyethylenimine (PEI).
1
PEI is the most well-known cationic
synthetic polymer composed of a high amount of secondary and
tertiary amines. Crowed secondary and tertiary amines in PEI show
a good buffering capacity in the weakly acidic pH. In the endosome,
PEI promotes proton and chloride anion entry, which induces
osmotic swelling of the endosome and the subsequent cargo release
into the cytoplasm.
1, 48
This is the so-called proton sponge effect.
PLGA is one of the first polymers approved by the US Food and Drug
Administration for human clinical use and it is both biocompatible
and biodegradable.
Since PLGA is hydrolyzed over time into
natural metabolic products, i.e., glycolic acid and lactic acid, PLGA-
based nanocarriers have been considered to have excellent safety
profiles.
24
49-51
Also, several studies on PLGA NPs suggested that the
encapsulation efficiency of nucleic acid could be enhanced in addition
to the sustained release and improved transfection efficiency by
incorporating them with other polymers, such as those containing
tertiary amines.
52-54
In recent years, inorganic nanomaterials have attracted much
attention as novel nucleic acid carriers thanks to the technological
advances in fabricating inorganic nanomaterials. Furthermore, the
surface of NPs can be readily functionalized with other polymers or
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