251
cal conditions to the active alkylating agent MTIC, has demonstrated
schedule-dependent antitumor activity against a variety of malignancies, including glioma, metastatic melanoma, and other difficult-to-treat cancers [32]. β-Cyclodextrin and diphenyl carbonate
as starting materials for NS were synthesized to fabricate a novel
drug delivery system for the treatment of brain tumors. Successful
loading of TMZ in prepared NS was confirmed using solution state
interaction studies wherein shift in wavelength of TMZ with
increasing concentration of NS indicated masking of hydrophobic
groups. In vitro release profile studies showed slow release of
TMZ. FTIR and NMR confirmed complexation. DSC and XRD
studies showed masking of TMZ crystallinity after loading into
prepared NSs. Activity of developed NS was assessed on U-373
glioma cell line by performing SRB assay, cell viability studies performed demonstrated cytotoxicity activity similar to that of pure
drug, and morphological investigations of the cells revealed degeneration/distortion of the cell structure [33].
Curcumin is a polyphenolic compound, naturally occurring in
turmeric spice, having potential application in tumor treatment but
has limited therapeutic utility because of its poor aqueous solubility at acidic and neutral pH, while it is soluble in alkali media [34].
Cyclodextrin-based nanosponges (NS) were obtained with
dimethyl carbonate as a cross-linker. The complex of curcumin
with NS (CrNS) was able to increase the therapeutic utility and
improve the solubility of curcumin by encapsulating it within the
internal cavity characterized for FTIR, XRD, and DSC studies.
The particle size of CrNS was found to be 487.3 nm with minimum polydispersity index of 0.476 and zeta potential of −27 mV
indicated formation of a stable colloidal nanosuspension. CrNS has
shown more solubilization efficiency (20.89 μg/mL) in comparison with plain curcumin (0.4 μg/mL) and β-CD NS (5.88 μg/
mL). In vitro drug release of curcumin was controlled over a prolonged period of time; hemolysis study showed that the complex
was non-hemolytic. CrNS sample showed only a slight reduction
in cytotoxicity against MCF-7 cells indicating no change in molecular structure of curcumin in CrNS formulation [34].
Sorafenib (SFN), class II drug, is an oral multikinase inhibitor
approved for the treatment of patients with advanced renal cell
carcinoma or unresectable hepatocellular carcinoma. SFN displays
antitumor activity across a variety of tumor types, including renal,
hepatocellular, breast, thyroid, and colorectal carcinomas. SFN is
water soluble at a rate of 9.86 ng/mL in a neutral pH environment
and its oral bioavailability is low (about 8.5%) due to its low aqueous solubility [35].
Inclusion complexes of β-CyD polymer and oligomer with
SFN have been studied as drug carriers. Water-soluble polymer
pCyD (92 kDa, 70% of CyDs, 57 CyD units) was purchased from
CyClolab and CyD oligomer (oCyD, 12 kDa, 65% of CyD, 7CyD
Drug-Encapsulated Cyclodextrin Nanosponges
cal conditions to the active alkylating agent MTIC, has demonstrated
schedule-dependent antitumor activity against a variety of malignancies, including glioma, metastatic melanoma, and other difficult-to-treat cancers [32]. β-Cyclodextrin and diphenyl carbonate
as starting materials for NS were synthesized to fabricate a novel
drug delivery system for the treatment of brain tumors. Successful
loading of TMZ in prepared NS was confirmed using solution state
interaction studies wherein shift in wavelength of TMZ with
increasing concentration of NS indicated masking of hydrophobic
groups. In vitro release profile studies showed slow release of
TMZ. FTIR and NMR confirmed complexation. DSC and XRD
studies showed masking of TMZ crystallinity after loading into
prepared NSs. Activity of developed NS was assessed on U-373
glioma cell line by performing SRB assay, cell viability studies performed demonstrated cytotoxicity activity similar to that of pure
drug, and morphological investigations of the cells revealed degeneration/distortion of the cell structure [33].
Curcumin is a polyphenolic compound, naturally occurring in
turmeric spice, having potential application in tumor treatment but
has limited therapeutic utility because of its poor aqueous solubility at acidic and neutral pH, while it is soluble in alkali media [34].
Cyclodextrin-based nanosponges (NS) were obtained with
dimethyl carbonate as a cross-linker. The complex of curcumin
with NS (CrNS) was able to increase the therapeutic utility and
improve the solubility of curcumin by encapsulating it within the
internal cavity characterized for FTIR, XRD, and DSC studies.
The particle size of CrNS was found to be 487.3 nm with minimum polydispersity index of 0.476 and zeta potential of −27 mV
indicated formation of a stable colloidal nanosuspension. CrNS has
shown more solubilization efficiency (20.89 μg/mL) in comparison with plain curcumin (0.4 μg/mL) and β-CD NS (5.88 μg/
mL). In vitro drug release of curcumin was controlled over a prolonged period of time; hemolysis study showed that the complex
was non-hemolytic. CrNS sample showed only a slight reduction
in cytotoxicity against MCF-7 cells indicating no change in molecular structure of curcumin in CrNS formulation [34].
Sorafenib (SFN), class II drug, is an oral multikinase inhibitor
approved for the treatment of patients with advanced renal cell
carcinoma or unresectable hepatocellular carcinoma. SFN displays
antitumor activity across a variety of tumor types, including renal,
hepatocellular, breast, thyroid, and colorectal carcinomas. SFN is
water soluble at a rate of 9.86 ng/mL in a neutral pH environment
and its oral bioavailability is low (about 8.5%) due to its low aqueous solubility [35].
Inclusion complexes of β-CyD polymer and oligomer with
SFN have been studied as drug carriers. Water-soluble polymer
pCyD (92 kDa, 70% of CyDs, 57 CyD units) was purchased from
CyClolab and CyD oligomer (oCyD, 12 kDa, 65% of CyD, 7CyD
Drug-Encapsulated Cyclodextrin Nanosponges