311
charge were prepared. The nanoparticles showed a prominent capacity of incorporating insulin. In vitro release study showed significant release rate of insulin under
acidic conditions than physiological conditions. In vitro cytotoxic evaluation against
Caco-2 cells exhibited that hyperbranched polyglycerol-β-cyclodextrin had significant biocompatibility. Moreover, the capacity of hyperbranched polyglycerol-βcyclodextrin nanoparticles to penetrate the nasal mucosal epithelia was proved by
confocal laser scanning microscopy.
Three alkyl carbonates of γ-cyclodextrin (hexyl-,octyl-, and dodecyl-carbonate)
have also been examined as a formulation additive to prepare solid nanoparticles for
the effective delivery of progesterone. They have developed spherical nanoparticles
in the size range of 80–200 nm. The prepared nanoparticles when subjected to evaluation showed negative surface charges and extended release rate of progesterone
(Cavalli et al. 2007). Glutathione is the main thiolated small peptide in mammalian
cells. It possesses reducing and nucleophilic properties which enable glutathione a
key redox buffer to inhibit the oxidative damage caused by free radicals. Glutathione
is used for the treatment of drug poisoning and protection against cytotoxic chemotherapy and radiation trauma. However, its clinical use encounters many hurdles
associated with its low and variable oral bioavailability, non-enzymatic pHdependent oxidation, and chemical and enzymatic degradation of the peptide in the
jejunum. Hence, inclusion and preservation of glutathione into conventional pharmaceutical dosage forms are challenging tasks Currently, glutathione is only available on the market as parenteral dosage forms (Gluthion) (Langie et al. 2007).
Therefore, to resolve these issues, Trapani et al. (2010) have developed new
nanoparticles containing chitosan or cyclodextrin and evaluate their potential for
oral delivery of the peptide glutathione. More precisely, nanoparticle formulations
composed of chitosan, chitosan/alpha-cyclodextrin, and chitosan/sulphobutyletherβ- cyclodextrin were investigated for this application. They have demonstrated that
by selecting the most suitable cyclodextrin, physicochemical characteristics of the
nanoparticles and their ability to load glutathione can be altered. Chitosan nanoparticles containing the anionic cyclodextrin sulfobutylether 7 m-β-cyclodextrin seem
to be significant potential oral glutathione carriers, as they combine enhanced glutathione loading along with the ability to improve glutathione permeabilization
through the intestine, as observed in a frog intestinal sac model.
Zhang et al. (2009) have demonstrated the feasibility of chitosan bearing
β-cyclodextrin nanocomplexes for controlled protein release. Briefly, chitosan bearing β-cyclodextrin nanocomplexes was fabricated by a single-step scheme with
N-succinylated chitosan and mono(6-(2-aminoethyl)amino-6-deoxy)-β-cyclodextrin
along with water-soluble carbodiimide. The results of in vitro cytotoxicity against
NIH 3 T3 cells confirmed that prepared nanocomplexes have not cytotoxic effect. In
conclusion, these results proved chitosan bearing β-cyclodextrin copolymer as a
novel carrier for controlled protein release.
More recently, He et al. (2019) reported a novel oral protein delivery system of
ovalbumin with improved intestinal permeability and enhanced antigen stability.
The delivery system based on the combination of chitosan nanoparticles and
antigen- cyclodextrin inclusion complex was prepared by a precipitation/
7 Role of Cyclodextrins in Nanoparticle-Based Systems for Drug Delivery
charge were prepared. The nanoparticles showed a prominent capacity of incorporating insulin. In vitro release study showed significant release rate of insulin under
acidic conditions than physiological conditions. In vitro cytotoxic evaluation against
Caco-2 cells exhibited that hyperbranched polyglycerol-β-cyclodextrin had significant biocompatibility. Moreover, the capacity of hyperbranched polyglycerol-βcyclodextrin nanoparticles to penetrate the nasal mucosal epithelia was proved by
confocal laser scanning microscopy.
Three alkyl carbonates of γ-cyclodextrin (hexyl-,octyl-, and dodecyl-carbonate)
have also been examined as a formulation additive to prepare solid nanoparticles for
the effective delivery of progesterone. They have developed spherical nanoparticles
in the size range of 80–200 nm. The prepared nanoparticles when subjected to evaluation showed negative surface charges and extended release rate of progesterone
(Cavalli et al. 2007). Glutathione is the main thiolated small peptide in mammalian
cells. It possesses reducing and nucleophilic properties which enable glutathione a
key redox buffer to inhibit the oxidative damage caused by free radicals. Glutathione
is used for the treatment of drug poisoning and protection against cytotoxic chemotherapy and radiation trauma. However, its clinical use encounters many hurdles
associated with its low and variable oral bioavailability, non-enzymatic pHdependent oxidation, and chemical and enzymatic degradation of the peptide in the
jejunum. Hence, inclusion and preservation of glutathione into conventional pharmaceutical dosage forms are challenging tasks Currently, glutathione is only available on the market as parenteral dosage forms (Gluthion) (Langie et al. 2007).
Therefore, to resolve these issues, Trapani et al. (2010) have developed new
nanoparticles containing chitosan or cyclodextrin and evaluate their potential for
oral delivery of the peptide glutathione. More precisely, nanoparticle formulations
composed of chitosan, chitosan/alpha-cyclodextrin, and chitosan/sulphobutyletherβ- cyclodextrin were investigated for this application. They have demonstrated that
by selecting the most suitable cyclodextrin, physicochemical characteristics of the
nanoparticles and their ability to load glutathione can be altered. Chitosan nanoparticles containing the anionic cyclodextrin sulfobutylether 7 m-β-cyclodextrin seem
to be significant potential oral glutathione carriers, as they combine enhanced glutathione loading along with the ability to improve glutathione permeabilization
through the intestine, as observed in a frog intestinal sac model.
Zhang et al. (2009) have demonstrated the feasibility of chitosan bearing
β-cyclodextrin nanocomplexes for controlled protein release. Briefly, chitosan bearing β-cyclodextrin nanocomplexes was fabricated by a single-step scheme with
N-succinylated chitosan and mono(6-(2-aminoethyl)amino-6-deoxy)-β-cyclodextrin
along with water-soluble carbodiimide. The results of in vitro cytotoxicity against
NIH 3 T3 cells confirmed that prepared nanocomplexes have not cytotoxic effect. In
conclusion, these results proved chitosan bearing β-cyclodextrin copolymer as a
novel carrier for controlled protein release.
More recently, He et al. (2019) reported a novel oral protein delivery system of
ovalbumin with improved intestinal permeability and enhanced antigen stability.
The delivery system based on the combination of chitosan nanoparticles and
antigen- cyclodextrin inclusion complex was prepared by a precipitation/
7 Role of Cyclodextrins in Nanoparticle-Based Systems for Drug Delivery