309
Nanotechnology-based drug delivery system provides an exceptional platform
for the delivery of anticancer agents in order to enhance their targeting ability and
bioavailability. One of the main advantages of loading anticancer drugs into
nanoparticles is to enhance their cellular uptakes by bypassing the different
multidrug- resistant mechanisms. Nanoparticle-based targeting of tumor cells has
emerged as a potential therapeutic arsenal against cancer. For example, paclitaxel
isolated from Taxus brevifolia is a potent anticancer agent approved for the treatment of a large number of solid tumors. But its hydrophobic nature results in low
bioavailability.
Therefore, to overcome the issue of hydrophobicity, Bilensoy and co-workers
have developed amphiphilic cyclodextrin as a nanoparticulate carrier system for
paclitaxel drug delivery. This yielded nanospheres via nanoprecipitation technique
with good cytotoxicity against L929 cells and was well studied using atomic force
microscopy micrographs (Bilensoy et al. 2008a, b). Further studies demonstrated
high encapsulation efficiency and a threefold increase in the loading capacity of
nanoparticles when formed directly from the inclusion complex. Prolonged release
rates for the drug were obtained: 12 h for nanospheres and 24 h for nanocapsules. In
another approach Agüeros et al. (2009) investigated the concept of utilizing
cyclodextrin- polyanhydride nanoparticles for oral delivery of paclitaxel. The addition of cyclodextrin increases the solubility by developing an inclusion complex,
and the use of polyanhydride enhances the intestinal permeability. Additionally,
they have also performed oral bioavailability studies in rodents by producing a synergistic effect using three distinct cyclodextrins, particularly β-cyclodextrin,
2-hydroxypropyl-β-cyclodextrin, and 6-mono-deoxy-6-monoamino-β-cyclodextrin
in the combination of polyanhydride nanoparticles.
7.2.2 Proteins and Peptides
Various problems associated with the practical use of therapeutic peptides and proteins are their chemical and enzymatic instability, poor absorption through biological membranes, rapid plasma clearance, peculiar dose-response curves, and
immunogenicity. Cyclodextrins, because of their adaptability in pharmaceutical use
and ability to interact with cellular membranes, can act as potential carriers for the
delivery of proteins, peptides, and oligonucleotide drugs (Irie and Uekama 1997).
The combination between cyclodextrins and nanoparticles can also be of interest for
the delivery of proteins and peptides. Cyclodextrin complexation represents an
effective strategy for improving protein therapy by stabilizing them against aggregation, thermal denaturation, and degradation. Proteins are mostly hydrophilic and
too bulky to be wholly included in the cavity of cyclodextrins. Nevertheless, the
hydrophobic side chains in the peptides may penetrate into the cavity of the oligosaccharide, leading to the formation of non-covalent inclusion complexes, which
improves the stability of proteins.
7 Role of Cyclodextrins in Nanoparticle-Based Systems for Drug Delivery
Nanotechnology-based drug delivery system provides an exceptional platform
for the delivery of anticancer agents in order to enhance their targeting ability and
bioavailability. One of the main advantages of loading anticancer drugs into
nanoparticles is to enhance their cellular uptakes by bypassing the different
multidrug- resistant mechanisms. Nanoparticle-based targeting of tumor cells has
emerged as a potential therapeutic arsenal against cancer. For example, paclitaxel
isolated from Taxus brevifolia is a potent anticancer agent approved for the treatment of a large number of solid tumors. But its hydrophobic nature results in low
bioavailability.
Therefore, to overcome the issue of hydrophobicity, Bilensoy and co-workers
have developed amphiphilic cyclodextrin as a nanoparticulate carrier system for
paclitaxel drug delivery. This yielded nanospheres via nanoprecipitation technique
with good cytotoxicity against L929 cells and was well studied using atomic force
microscopy micrographs (Bilensoy et al. 2008a, b). Further studies demonstrated
high encapsulation efficiency and a threefold increase in the loading capacity of
nanoparticles when formed directly from the inclusion complex. Prolonged release
rates for the drug were obtained: 12 h for nanospheres and 24 h for nanocapsules. In
another approach Agüeros et al. (2009) investigated the concept of utilizing
cyclodextrin- polyanhydride nanoparticles for oral delivery of paclitaxel. The addition of cyclodextrin increases the solubility by developing an inclusion complex,
and the use of polyanhydride enhances the intestinal permeability. Additionally,
they have also performed oral bioavailability studies in rodents by producing a synergistic effect using three distinct cyclodextrins, particularly β-cyclodextrin,
2-hydroxypropyl-β-cyclodextrin, and 6-mono-deoxy-6-monoamino-β-cyclodextrin
in the combination of polyanhydride nanoparticles.
7.2.2 Proteins and Peptides
Various problems associated with the practical use of therapeutic peptides and proteins are their chemical and enzymatic instability, poor absorption through biological membranes, rapid plasma clearance, peculiar dose-response curves, and
immunogenicity. Cyclodextrins, because of their adaptability in pharmaceutical use
and ability to interact with cellular membranes, can act as potential carriers for the
delivery of proteins, peptides, and oligonucleotide drugs (Irie and Uekama 1997).
The combination between cyclodextrins and nanoparticles can also be of interest for
the delivery of proteins and peptides. Cyclodextrin complexation represents an
effective strategy for improving protein therapy by stabilizing them against aggregation, thermal denaturation, and degradation. Proteins are mostly hydrophilic and
too bulky to be wholly included in the cavity of cyclodextrins. Nevertheless, the
hydrophobic side chains in the peptides may penetrate into the cavity of the oligosaccharide, leading to the formation of non-covalent inclusion complexes, which
improves the stability of proteins.
7 Role of Cyclodextrins in Nanoparticle-Based Systems for Drug Delivery