curcumin onto chitosan-g-poly(N-isopropylacrylamide) and chitosan-g-poly
(N-vinylcaprolactam) and showed the in vitro cellular uptake by the cancer cells
by virtue of the intrinsic fluorescence property of curcumin. The cytotoxicity assay
was carried out at the lower critical solution temperature (LCST) of 38
C and below
LCST (35
C) and showed enhanced cancer cell death at LCST, indicating the
temperature-sensitive release of the drug, inducing toxicity to breast and prostate
cancer cells [138, 139].
Curcumin encapsulated in b-cyclodextrin (CD30) was evaluated for its intracellular uptake and anticancer activity towards prostate cancer cells (C4-2 and
DU145). The IC 50 of CD30 is 16.8 in C4-2 cancer cells and 17.6 mM in DU145
cancer cells, values that are comparable to that of free curcumin. Cells treated with
2–10 mM CD30 formed fewer colonies (as shown by colony formation assays) over
a 10-day period. Cell proliferation and clonogenic assays demonstrated that
b-cyclodextrin–curcumin self-assembly enhanced curcumin delivery and improved
its therapeutic efficacy in prostate cancer cells compared to free curcumin [140].
Dhule et al. reported cyclodextrin-based liposomes for the delivery of curcumin
against osteosarcoma after evaluation against cancer models of mesenchymal (OS)
and epithelial origin (breast cancer). Curcumin encapsulated in cyclodextrins
followed by a second encapsulation in liposomes (i.e. 2-hydroxypropyl-g-cyclodextrin/curcumin–liposome complex) shows promising anticancer potential both
in vitro and in vivo against a KHOS OS cell line and a MCF-7 breast cancer cell
line. The curcumin solubilization and entrapment was enhanced by cyclodextrin
complexation. Liposomal curcumin initiates the caspase cascade that leads to
apoptotic cell death in vitro. The efficiency of the liposomal curcumin formulation
was also confirmed in vivo using a xenograft OS model [141].
The free network structures throughout the crosslinked copolymer nanogels
offer the opportunity to load various types of lipophilic drug molecules [142].
Bisht et al. [143] tested the effects of hydrogel nanocurcumin prepared by the
redox free-radical polymerization of N-isopropylacrylamide and N-vinyl-2pyrrolidone in the presence of PEG monoacrylate on pancreatic cancer cell lines.
Nanocurcumin blocked the activation of NF-kB, downregulated steady-state
transcripts of multiple pro-inflammatory cytokines and inhibited IL-6 synthesis.
The tumor growth was significantly inhibited by parenteral administration of the
hydrogel nanocurcumin formulation in both subcutaneous and orthotopic settings in
xenograft models of human pancreatic cancer in athymic mice. Also, treatment with
gemcitabine combined with hydrogel promoted an enhanced tumor growth inhibition capacity [143]. The hydrogel formulation was found to be effective in
inhibiting the proliferation and clonogenicity of medulloblastoma and glioblastoma
cell lines. The formulation has achieved a dose-dependent antiproliferation effect in
embryonal tumor-derived lines DAOY and D283Med, and the glioblastoma
neurosphere lines HSR-GBM1 and JHH-GBM14 [144]. A series of curcuminloaded dextran-modified hydrogel NPs were studied by Goncalves et al. [145]. A
water-dispersible hybrid nanogel for intracellular delivery of curcumin was developed by Wu et al. [147]. The core–shell structured hybrid nanogels were
synthesized by coating the Ag/Au bimetallic NPs with a hydrophobic polystyrene
Phytomedicine-Loaded Polymeric Nanomedicines: Potential Cancer Therapeutics
221
(N-vinylcaprolactam) and showed the in vitro cellular uptake by the cancer cells
by virtue of the intrinsic fluorescence property of curcumin. The cytotoxicity assay
was carried out at the lower critical solution temperature (LCST) of 38
C and below
LCST (35
C) and showed enhanced cancer cell death at LCST, indicating the
temperature-sensitive release of the drug, inducing toxicity to breast and prostate
cancer cells [138, 139].
Curcumin encapsulated in b-cyclodextrin (CD30) was evaluated for its intracellular uptake and anticancer activity towards prostate cancer cells (C4-2 and
DU145). The IC 50 of CD30 is 16.8 in C4-2 cancer cells and 17.6 mM in DU145
cancer cells, values that are comparable to that of free curcumin. Cells treated with
2–10 mM CD30 formed fewer colonies (as shown by colony formation assays) over
a 10-day period. Cell proliferation and clonogenic assays demonstrated that
b-cyclodextrin–curcumin self-assembly enhanced curcumin delivery and improved
its therapeutic efficacy in prostate cancer cells compared to free curcumin [140].
Dhule et al. reported cyclodextrin-based liposomes for the delivery of curcumin
against osteosarcoma after evaluation against cancer models of mesenchymal (OS)
and epithelial origin (breast cancer). Curcumin encapsulated in cyclodextrins
followed by a second encapsulation in liposomes (i.e. 2-hydroxypropyl-g-cyclodextrin/curcumin–liposome complex) shows promising anticancer potential both
in vitro and in vivo against a KHOS OS cell line and a MCF-7 breast cancer cell
line. The curcumin solubilization and entrapment was enhanced by cyclodextrin
complexation. Liposomal curcumin initiates the caspase cascade that leads to
apoptotic cell death in vitro. The efficiency of the liposomal curcumin formulation
was also confirmed in vivo using a xenograft OS model [141].
The free network structures throughout the crosslinked copolymer nanogels
offer the opportunity to load various types of lipophilic drug molecules [142].
Bisht et al. [143] tested the effects of hydrogel nanocurcumin prepared by the
redox free-radical polymerization of N-isopropylacrylamide and N-vinyl-2pyrrolidone in the presence of PEG monoacrylate on pancreatic cancer cell lines.
Nanocurcumin blocked the activation of NF-kB, downregulated steady-state
transcripts of multiple pro-inflammatory cytokines and inhibited IL-6 synthesis.
The tumor growth was significantly inhibited by parenteral administration of the
hydrogel nanocurcumin formulation in both subcutaneous and orthotopic settings in
xenograft models of human pancreatic cancer in athymic mice. Also, treatment with
gemcitabine combined with hydrogel promoted an enhanced tumor growth inhibition capacity [143]. The hydrogel formulation was found to be effective in
inhibiting the proliferation and clonogenicity of medulloblastoma and glioblastoma
cell lines. The formulation has achieved a dose-dependent antiproliferation effect in
embryonal tumor-derived lines DAOY and D283Med, and the glioblastoma
neurosphere lines HSR-GBM1 and JHH-GBM14 [144]. A series of curcuminloaded dextran-modified hydrogel NPs were studied by Goncalves et al. [145]. A
water-dispersible hybrid nanogel for intracellular delivery of curcumin was developed by Wu et al. [147]. The core–shell structured hybrid nanogels were
synthesized by coating the Ag/Au bimetallic NPs with a hydrophobic polystyrene
Phytomedicine-Loaded Polymeric Nanomedicines: Potential Cancer Therapeutics
221