272
gen release determination. Later, the three different formulations
were tested at 0.2, 2, and 20 μg/mL to ascertain their capability to
reduce cell mortality during hypoxia and reoxygenation (H/R) in
vitro protocols. H9c2, a cardiomyoblast cell line, was exposed to
normoxia (20% O 2 ) or hypoxia (5% CO 2 and 95% N 2 ). The different
formulations, applied before hypoxia, induced a significant reduction in cell mortality (in a range of 15–30%) when compared to
samples devoid of oxygen. Moreover, their application at the
beginning of reoxygenation induced a considerable reduction in
cell death (12–20%). α-CD NS showed a marked efficacy in controlled oxygenation, which suggests an interesting potential for
future medical application of polymer systems for myocardial
infarction (MI) treatment [97].
Repaglinide is an oral hypoglycemic agent that belongs to the
short-acting insulin secretagogues, which act by binding to β cells
of the pancreas to stimulate insulin release. The side effects of repaglinide may be due its acid–base ampholyte character (pKa1 = 4.2;
pKa2 = 6.0) with low water solubility (34 μg/mL at 37 °C) and
high lipophilicity (log P = 3.97) [98]. Earlier studies focused on
the possibilities to improve pharmacokinetic characteristics of repaglinide using β-CD and several substituted derivatives. Polymeric
nanostructures derived from sulfobutylether β-cyclodextrin (SBE
β-CD) are less investigated because of the characteristic high
degree of substitution which results in less possibilities to bond the
cyclodextrin toroid. β-CD-NS and SBE β-CD-NS were synthesized (1:10 CD/cross-linker ratio). These NS and their complexes
with repaglinide (5:1 NS:repaglinide) were characterized and solubility was studied following Higuchi and Connors method, which
provided higher solubilization of repaglinide. Though its loading
capacity is significantly higher, the lower solubilization effect of
SBE β-CD-NS is probably due to a steric hindrance. The high
degree of substitution of SBE β-CD allows a small number of
intermolecular bonds and a less reticulated structure (i.e., lower
entrapment of the guest molecules) [99].
Atorvastatin calcium (AC) is a synthetic drug, assigned to class II
with high permeability and low aqueous solubility (log p¼ 5.39)
that result in poor dissolution in the biological fluid and hence
limited oral bioavailability. AC can selectively and competitively
inhibit hydroxymethyl glutaryl-coenzyme A (HMG-CoA) reductase enzyme that catalyzes the conversion of HMG-CoA to mevalonate, an early and a rate-limiting step in the biosynthesis of
cholesterol; thus AC plays an important role in treatment and prevention of hyperlipidemia-associated diseases [100].
CD-based NSs cross-linked with carbonyldiimidazole (ratios
1:2, 1:4, and 1:8) developed by solvent method were used to form
AC-NS complexes to improve oral absorption and bioavailability
2.15 Cyclodextrin
Nanosponges
for Antihyperglycemic
Agent
2.16 Cyclodextrin
Nanosponges
for Calcium Delivery
Maria Tannous et al.
gen release determination. Later, the three different formulations
were tested at 0.2, 2, and 20 μg/mL to ascertain their capability to
reduce cell mortality during hypoxia and reoxygenation (H/R) in
vitro protocols. H9c2, a cardiomyoblast cell line, was exposed to
normoxia (20% O 2 ) or hypoxia (5% CO 2 and 95% N 2 ). The different
formulations, applied before hypoxia, induced a significant reduction in cell mortality (in a range of 15–30%) when compared to
samples devoid of oxygen. Moreover, their application at the
beginning of reoxygenation induced a considerable reduction in
cell death (12–20%). α-CD NS showed a marked efficacy in controlled oxygenation, which suggests an interesting potential for
future medical application of polymer systems for myocardial
infarction (MI) treatment [97].
Repaglinide is an oral hypoglycemic agent that belongs to the
short-acting insulin secretagogues, which act by binding to β cells
of the pancreas to stimulate insulin release. The side effects of repaglinide may be due its acid–base ampholyte character (pKa1 = 4.2;
pKa2 = 6.0) with low water solubility (34 μg/mL at 37 °C) and
high lipophilicity (log P = 3.97) [98]. Earlier studies focused on
the possibilities to improve pharmacokinetic characteristics of repaglinide using β-CD and several substituted derivatives. Polymeric
nanostructures derived from sulfobutylether β-cyclodextrin (SBE
β-CD) are less investigated because of the characteristic high
degree of substitution which results in less possibilities to bond the
cyclodextrin toroid. β-CD-NS and SBE β-CD-NS were synthesized (1:10 CD/cross-linker ratio). These NS and their complexes
with repaglinide (5:1 NS:repaglinide) were characterized and solubility was studied following Higuchi and Connors method, which
provided higher solubilization of repaglinide. Though its loading
capacity is significantly higher, the lower solubilization effect of
SBE β-CD-NS is probably due to a steric hindrance. The high
degree of substitution of SBE β-CD allows a small number of
intermolecular bonds and a less reticulated structure (i.e., lower
entrapment of the guest molecules) [99].
Atorvastatin calcium (AC) is a synthetic drug, assigned to class II
with high permeability and low aqueous solubility (log p¼ 5.39)
that result in poor dissolution in the biological fluid and hence
limited oral bioavailability. AC can selectively and competitively
inhibit hydroxymethyl glutaryl-coenzyme A (HMG-CoA) reductase enzyme that catalyzes the conversion of HMG-CoA to mevalonate, an early and a rate-limiting step in the biosynthesis of
cholesterol; thus AC plays an important role in treatment and prevention of hyperlipidemia-associated diseases [100].
CD-based NSs cross-linked with carbonyldiimidazole (ratios
1:2, 1:4, and 1:8) developed by solvent method were used to form
AC-NS complexes to improve oral absorption and bioavailability
2.15 Cyclodextrin
Nanosponges
for Antihyperglycemic
Agent
2.16 Cyclodextrin
Nanosponges
for Calcium Delivery
Maria Tannous et al.