312
coacervation method. Results of the in vivo study of nanoparticles revealed that
ovalbumin-loaded cyclodextrin/chitosan nanoparticles possess the capacity to
induce an intestinal mucosal immune response.
7.3 Cyclodextrin Nanoparticles as Gene Delivery Systems
Gene therapy as an option to conventional drug therapy paves the new way for the
treatment of both genetic and inherited diseases, such as hemophilia, cystic fibrosis,
and cancers. The efficacy of a viral or non-viral vector directly determines the benefit of gene therapy. Gene therapy offer advantages over conventional protein therapy such as improved bioavailability and reduced systemic toxicity. Therefore, to
avoid the toxicity issue of viral vectors, researchers have developed cyclodextrinbased nanoparticles as non-viral vectors. The unique characteristic of the presence
of two well-differentiated faces in the cyclodextrins, specifically the narrower rim
owning the primary hydroxyl groups and the wider rim positioning two chemically
distinct sets of secondary hydroxyls, is an intrinsic characteristic of this family of
cyclo-oligosaccharides that classifies them as genuine Janus (the Roman god of
doorways and passages, depicted with two faces on opposite sides of his head)
molecular nanoparticles.
In 1999, Gonzalez et al. (1999) published the first report of the synthesis of the
cationic cyclodextrin polymers and the characterization of the cationic cyclodextrin
nanoparticles loaded with plasmid DNA including their in vitro transfection efficiency. Teijeiro-Osorio et al. (2009) first reported the potential of a new generation
of hybrid polysaccharide nanocarriers composed of chitosan and anionic cyclodextrins for gene delivery to the airway epithelium. They investigated hybrid polysaccharide nanocarriers to evaluate their ability to penetrate epithelial cells and improve
gene expression in the Calu-3 cell culture model. Furthermore, hybrid chitosan and
anionic cyclodextrin nanoparticles were developed and loaded with plasmid DNA
model that encodes the expression of secreted alkaline phosphatase. Results of cellular uptake studies revealed that the nanoparticles were efficiently internalized by
the cells and confirm their potential as gene vectors. The transfection ability of the
various nanoparticle formulations showed a significantly higher response than the
naked DNA (control). This resulted in enhanced delivery of DNA and reduces the
otherwise high levels of protein expression in the respiratory mucosa.
Similarly, cyclodextrin-based polycations have also been studied for nucleic acid
delivery. Park et al. (2006) have demonstrated a new strategy for surface-mediated
gene delivery based on inclusion complex formation between the solid surface and
delivery carrier. The complexation ability of β-cyclodextrin molecule was utilized
to especially immobilize cyclodextrin-modified polyethylenimine nanoparticles, on
adamantane-altered self-assembled monolayers. Cyclodextrin-modified polyethylenimine nanoparticles are particularly immobilized on the chip surface by
cyclodextrin- adamantane inclusion complex formation. The results of competition
studies with free cyclodextrins showed multivalent interactions between
A. Pandey
coacervation method. Results of the in vivo study of nanoparticles revealed that
ovalbumin-loaded cyclodextrin/chitosan nanoparticles possess the capacity to
induce an intestinal mucosal immune response.
7.3 Cyclodextrin Nanoparticles as Gene Delivery Systems
Gene therapy as an option to conventional drug therapy paves the new way for the
treatment of both genetic and inherited diseases, such as hemophilia, cystic fibrosis,
and cancers. The efficacy of a viral or non-viral vector directly determines the benefit of gene therapy. Gene therapy offer advantages over conventional protein therapy such as improved bioavailability and reduced systemic toxicity. Therefore, to
avoid the toxicity issue of viral vectors, researchers have developed cyclodextrinbased nanoparticles as non-viral vectors. The unique characteristic of the presence
of two well-differentiated faces in the cyclodextrins, specifically the narrower rim
owning the primary hydroxyl groups and the wider rim positioning two chemically
distinct sets of secondary hydroxyls, is an intrinsic characteristic of this family of
cyclo-oligosaccharides that classifies them as genuine Janus (the Roman god of
doorways and passages, depicted with two faces on opposite sides of his head)
molecular nanoparticles.
In 1999, Gonzalez et al. (1999) published the first report of the synthesis of the
cationic cyclodextrin polymers and the characterization of the cationic cyclodextrin
nanoparticles loaded with plasmid DNA including their in vitro transfection efficiency. Teijeiro-Osorio et al. (2009) first reported the potential of a new generation
of hybrid polysaccharide nanocarriers composed of chitosan and anionic cyclodextrins for gene delivery to the airway epithelium. They investigated hybrid polysaccharide nanocarriers to evaluate their ability to penetrate epithelial cells and improve
gene expression in the Calu-3 cell culture model. Furthermore, hybrid chitosan and
anionic cyclodextrin nanoparticles were developed and loaded with plasmid DNA
model that encodes the expression of secreted alkaline phosphatase. Results of cellular uptake studies revealed that the nanoparticles were efficiently internalized by
the cells and confirm their potential as gene vectors. The transfection ability of the
various nanoparticle formulations showed a significantly higher response than the
naked DNA (control). This resulted in enhanced delivery of DNA and reduces the
otherwise high levels of protein expression in the respiratory mucosa.
Similarly, cyclodextrin-based polycations have also been studied for nucleic acid
delivery. Park et al. (2006) have demonstrated a new strategy for surface-mediated
gene delivery based on inclusion complex formation between the solid surface and
delivery carrier. The complexation ability of β-cyclodextrin molecule was utilized
to especially immobilize cyclodextrin-modified polyethylenimine nanoparticles, on
adamantane-altered self-assembled monolayers. Cyclodextrin-modified polyethylenimine nanoparticles are particularly immobilized on the chip surface by
cyclodextrin- adamantane inclusion complex formation. The results of competition
studies with free cyclodextrins showed multivalent interactions between
A. Pandey