Biomedical Engineering Reference
In-Depth Information
[79]. These nanoparticles shown improved skin penetration and
enhanced gene expression in comparison with nanoparticles solely
comprised of chitosan and DNA. This can be attributed to a greater
density of the gamma-poly-(glutamic acid)-containing nanoparticles,
which contributed to a larger penetration momentum into the skin
barrier. In a following study [80] the gamma-poly-(glutamic acid)-
containing nanoparticles showed a significant increase in cellular
uptake and transfection efficiency of HT1080 (human fibrosarcoma)
cells in comparison with DNA-chitosan nanoparticles. Another study
describing PEC of chitosan and DNA have reported by Krishnendu et
al. [81] who have shown that theses PEC can generate immunologic
protection in a murine model of peanut allergy. The mice who received
nanoparticles containing a dominant peanut allergen gene produced
secretory IgA and serum IgG2a and showed a substantial reduction
in allergen-induced anaphylaxis associated with reduced levels of
IgE, plasma histamine and vascular leakage. More recently, plasmid-
chitosan PEC was applied in the delivery of FGF-2 and PDGF-BB
[82]. Plasmid-chitosan PEC containing FGF-2/PDGF-BB genes were
injected into BALB/C mice. Several formulations were tested, which
diff ered in the degree of chitosan deacetylation and Mw. ELISA assays
performed on mice sera showed FGF-2 and PDGF-BB expression. In
addition, induction of specific antibodies against these proteins has
been shown. PEC containing highly deacetylated low-Mw chitosan,
were found to efficiently induce protein expression with minimal
production of neutralizing antibodies, which was also confirmed by
histological analyses.
Recently, PEC of ultrapure chitosan monomers was used for
ocular gene delivery [83]. The nanoparticle preparation which was
based on a method developed by Koping-Hoggard et al. [84] had an
average size of ~ 100 nm in diameter and a strong positive charge.
This formulation demonstrated eff ective transfection of COS-7
cells
in vitro
and luciferase gene expression 5.4 times greater than
polyethylenimine-DNA nanoparticles upon injection to rat corneas.
The preparation method of PEC of chitosan and DNA was further
improved by Artursson, who optimized the balance between stability
and unpacking of PEC containing chitosan oligomers of diff erent sizes
[85]. PEC of chitosan oligomers and pDNA have several advantages
over PEC of high-Mw chitosan and pDNA: High-Mw chitosan form
extremely stable PEC with DNA, which delays the release of DNA and
therefore results in a slow onset of action. In addition, these PEC are
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