selectivity. The yields of 2
A ,2
D -disulfonates, 68, and 2
A ,2
C -disulfonates, 67, were
53% and 3.5%, respectively. For γ-CD, the yields of 2
A ,2
D -disulfonates, 70, and
2
A ,2
C -disulfonates, 69, were 37% and 4.0%, respectively. For α-CD, the yields of
2
A ,2
D -disulfonates, 66, and 2
A ,2
C -disulfonates, 65, were 16% and 3.8%, respectively. These results indicated that the authors had developed a disulfonyl imidazole
bridge strategy that not only could provide satisfactory regioselectivity and excellent
yields, especially for β-CD, but also two potential further modified positions. Thus,
the disulfonyl imidazole strategy was quite successful [23] (Scheme 14).
14.3 Applications of Cyclodextrins as Delivery Systems
Drugs and biosensors are not easy for our bodies to take up, because of their
chemical and physical properties that largely limit their utility for cure or detection
in our bodies. Even if we can inject them into our vessels, a lot of drugs and
biosensors do not work when injected into the blood directly; therefore, they need
delivery carriers to transport them to specific positions and release them. Though use
of cyclodextrins as pharmaceutical excipients has been studied extensively for the
past few decades, there are still some new applications to be explored, such as
molecular inclusion complex systems, nanocarrier systems, stimuli-responsive
delivery systems, and targeted delivery systems, which can improve the physicochemical stability, solubility, dissolution rate, and bioavailability of drugs.
14.3.1 Cyclodextrins as Gene Delivery Efficiency Enhancers
A liposome-mediated DNA delivery system is an efficient delivery method for gene
therapy. These nonviral carrier systems are absorbed by the membrane fluidity of
cells, which is known as endocytosis. The cell membrane fluidity is largely regulated
by cholesterol, which can be manipulated by methyl-β-cyclodextrin [25].
On the basis of this concept, Sakurai and coworkers used schizophyllan, a
polysaccharide consisting of a repeating unit that includes three glucoses conjugated
with a β(1–3)-D-glucan bone grafted to a glucose at the OH-6 position of the second
glucosyl residue, as the backbone to connect cholesterols. These derivatives can
form stable complexes with oligonucleotides (ONs) [26, 27], but at some densities of
cholesterol the formation kinetics are unfavorable, which may prevent the
schizophyllan derivatives and the ONs from forming complexes (Fig. 3). Therefore,
the authors added β-CD into the schizophyllan–cholesterol derivatives to control the
densities of cholesterol, and they then added the ONs to form a new species of the
complex, which improved the complexation ability, resulting in sufficient desired
complexes to achieve great cellular permeation ability [28, 29].
Small interfering RNAs (siRNAs) have proved to be efficient in cancer therapy,
but a major challenge for the use of siRNAs in humans is delivery of the siRNAs to
the target tissues and organs. Therefore, Ribas and coworkers designed and prepared
a nanoparticle transport system, including (1) a linear cyclodextrin-based polymer
14 Functionalized Cyclodextrins and Their Applications in Biodelivery
399
A ,2
D -disulfonates, 68, and 2
A ,2
C -disulfonates, 67, were
53% and 3.5%, respectively. For γ-CD, the yields of 2
A ,2
D -disulfonates, 70, and
2
A ,2
C -disulfonates, 69, were 37% and 4.0%, respectively. For α-CD, the yields of
2
A ,2
D -disulfonates, 66, and 2
A ,2
C -disulfonates, 65, were 16% and 3.8%, respectively. These results indicated that the authors had developed a disulfonyl imidazole
bridge strategy that not only could provide satisfactory regioselectivity and excellent
yields, especially for β-CD, but also two potential further modified positions. Thus,
the disulfonyl imidazole strategy was quite successful [23] (Scheme 14).
14.3 Applications of Cyclodextrins as Delivery Systems
Drugs and biosensors are not easy for our bodies to take up, because of their
chemical and physical properties that largely limit their utility for cure or detection
in our bodies. Even if we can inject them into our vessels, a lot of drugs and
biosensors do not work when injected into the blood directly; therefore, they need
delivery carriers to transport them to specific positions and release them. Though use
of cyclodextrins as pharmaceutical excipients has been studied extensively for the
past few decades, there are still some new applications to be explored, such as
molecular inclusion complex systems, nanocarrier systems, stimuli-responsive
delivery systems, and targeted delivery systems, which can improve the physicochemical stability, solubility, dissolution rate, and bioavailability of drugs.
14.3.1 Cyclodextrins as Gene Delivery Efficiency Enhancers
A liposome-mediated DNA delivery system is an efficient delivery method for gene
therapy. These nonviral carrier systems are absorbed by the membrane fluidity of
cells, which is known as endocytosis. The cell membrane fluidity is largely regulated
by cholesterol, which can be manipulated by methyl-β-cyclodextrin [25].
On the basis of this concept, Sakurai and coworkers used schizophyllan, a
polysaccharide consisting of a repeating unit that includes three glucoses conjugated
with a β(1–3)-D-glucan bone grafted to a glucose at the OH-6 position of the second
glucosyl residue, as the backbone to connect cholesterols. These derivatives can
form stable complexes with oligonucleotides (ONs) [26, 27], but at some densities of
cholesterol the formation kinetics are unfavorable, which may prevent the
schizophyllan derivatives and the ONs from forming complexes (Fig. 3). Therefore,
the authors added β-CD into the schizophyllan–cholesterol derivatives to control the
densities of cholesterol, and they then added the ONs to form a new species of the
complex, which improved the complexation ability, resulting in sufficient desired
complexes to achieve great cellular permeation ability [28, 29].
Small interfering RNAs (siRNAs) have proved to be efficient in cancer therapy,
but a major challenge for the use of siRNAs in humans is delivery of the siRNAs to
the target tissues and organs. Therefore, Ribas and coworkers designed and prepared
a nanoparticle transport system, including (1) a linear cyclodextrin-based polymer
14 Functionalized Cyclodextrins and Their Applications in Biodelivery
399