313
cyclodextrin-modified polyethylenimine nanoparticles and the adamantanemodified surface results in tremendous binding affinity. Therefore, the ability of
cyclodextrin-modified polyethylenimine nanoparticles to form inclusion complexes
can be employed to achieve specific, high-affinity loading of delivery carriers onto
solid surfaces.
Huntington’s disease is an uncommon autosomal neurodegenerative disease provoked by the expression of a toxic huntingtin protein. The huntingtin gene renders
instructions for producing a protein called huntingtin. This protein plays a vital role
in neurons in the brain and is essential for healthy growth before birth. The application of short interfering RNAs (siRNAs) is a promising approach to restrict the
mutation of protein. The main hindrance in siRNA-based strategies is the lack of
efficient and nontoxic transportation vectors to ensure target delivery to the nervous
system. This stimulated Godinho et al. (2013) to develop modified amphiphilic
β-cyclodextrins as novel siRNA neuronal carriers. The results showed that the
cyclodextrin formed nanosized particles were stable in artificial cerebrospinal fluid.
Furthermore, these complexes significantly reduced the expression of the huntingtin
gene in rat striatal cells and human Huntington’s disease primary fibroblasts. These
findings firmly support the utility of modified β-cyclodextrins as safe and effective
siRNA delivery vectors (Godinho et al. 2013).
Since the past few years, several strategies of low and high molecular weight
polyethylenimines have been attempted for safe and effective DNA and siRNA
delivery but were limited by transfection and cytotoxic activity. Therefore a
copolymer- based delivery system has been developed by researchers. Ping et al.
(2011) synthesized chitosan-graft-polyethylenimine-β-cyclodextrin copolymers for
DNA and siRNA delivery. These two hydrophilic cationic copolymers were fabricated by a reductive amination reaction between oxidized chitosan and low molecular weight polyethylenimine-modified β-cyclodextrin. Furthermore, the
characterization of nanoparticles was carried out by proton nuclear magnetic resonance spectroscopy and gel permeation chromatography. These polycations displayed significant ability to condense both plasmid DNA and small interfering RNA
into compact and spherical nanoparticles. Additionally, both polymers delineate
improved gene transfection activity performance in comparison with native CTS in
HEK293, L929, and COS7 cell lines.
In the past decade, low and high molecular weight polyethylenimines have been
extensively studied for DNA and siRNA delivery but have faced challenges of transfection and cytotoxic activity. A new strategy was suggested where polyplexes
formed between polymers and DNA were further enhanced by the addition of
β-cyclodextrin. In another laboratory work to facilitate the delivery of siRNA, cationic cyclodextrin conjugated with poly(ethylene glycol) (PEG) chain to expedite
the attachment of targeting group anisamide. Parenteral administration of anisamidetagged PEGylated cyclodextrin nanoparticles presented notable tumor inactivation
with diminished toxicity when investigated preclinically in a rodent prostate tumor
model. Hence, serving as an excellent drug delivery system of siRNA delivery for
prostate cancer therapy (Guo et al. 2012). The siRNAs generally exhibit weak cell
7 Role of Cyclodextrins in Nanoparticle-Based Systems for Drug Delivery
cyclodextrin-modified polyethylenimine nanoparticles and the adamantanemodified surface results in tremendous binding affinity. Therefore, the ability of
cyclodextrin-modified polyethylenimine nanoparticles to form inclusion complexes
can be employed to achieve specific, high-affinity loading of delivery carriers onto
solid surfaces.
Huntington’s disease is an uncommon autosomal neurodegenerative disease provoked by the expression of a toxic huntingtin protein. The huntingtin gene renders
instructions for producing a protein called huntingtin. This protein plays a vital role
in neurons in the brain and is essential for healthy growth before birth. The application of short interfering RNAs (siRNAs) is a promising approach to restrict the
mutation of protein. The main hindrance in siRNA-based strategies is the lack of
efficient and nontoxic transportation vectors to ensure target delivery to the nervous
system. This stimulated Godinho et al. (2013) to develop modified amphiphilic
β-cyclodextrins as novel siRNA neuronal carriers. The results showed that the
cyclodextrin formed nanosized particles were stable in artificial cerebrospinal fluid.
Furthermore, these complexes significantly reduced the expression of the huntingtin
gene in rat striatal cells and human Huntington’s disease primary fibroblasts. These
findings firmly support the utility of modified β-cyclodextrins as safe and effective
siRNA delivery vectors (Godinho et al. 2013).
Since the past few years, several strategies of low and high molecular weight
polyethylenimines have been attempted for safe and effective DNA and siRNA
delivery but were limited by transfection and cytotoxic activity. Therefore a
copolymer- based delivery system has been developed by researchers. Ping et al.
(2011) synthesized chitosan-graft-polyethylenimine-β-cyclodextrin copolymers for
DNA and siRNA delivery. These two hydrophilic cationic copolymers were fabricated by a reductive amination reaction between oxidized chitosan and low molecular weight polyethylenimine-modified β-cyclodextrin. Furthermore, the
characterization of nanoparticles was carried out by proton nuclear magnetic resonance spectroscopy and gel permeation chromatography. These polycations displayed significant ability to condense both plasmid DNA and small interfering RNA
into compact and spherical nanoparticles. Additionally, both polymers delineate
improved gene transfection activity performance in comparison with native CTS in
HEK293, L929, and COS7 cell lines.
In the past decade, low and high molecular weight polyethylenimines have been
extensively studied for DNA and siRNA delivery but have faced challenges of transfection and cytotoxic activity. A new strategy was suggested where polyplexes
formed between polymers and DNA were further enhanced by the addition of
β-cyclodextrin. In another laboratory work to facilitate the delivery of siRNA, cationic cyclodextrin conjugated with poly(ethylene glycol) (PEG) chain to expedite
the attachment of targeting group anisamide. Parenteral administration of anisamidetagged PEGylated cyclodextrin nanoparticles presented notable tumor inactivation
with diminished toxicity when investigated preclinically in a rodent prostate tumor
model. Hence, serving as an excellent drug delivery system of siRNA delivery for
prostate cancer therapy (Guo et al. 2012). The siRNAs generally exhibit weak cell
7 Role of Cyclodextrins in Nanoparticle-Based Systems for Drug Delivery