HCT116 (human colon adenocarcinoma), and SEG-1 (human esophageal adenocarcinoma) cell lines and showed superior bioavailability in vivo. NF-kB involved
in cell proliferation (cyclin D1), invasion (MMP-9), and angiogenesis (VEGF)
was inhibited by the nanocurcumin. The study also demonstrated that the nanoformulation increased the half life of curcumin and made it more bioavailable
in vivo [126]. The effectiveness of curcumin encapsulated in PLGA NPs (NanoCurc)
against hepatocellular carcinoma (HCC) has been evaluated using a rat model
with oral diethylnitrosamine (DEN)-induced HCC. The study reported that this
nanocurcumin was more effective than free curcumin as a free-radical quencher
in combating the oxidative damage of hepatic cells and prevented DEN-induced
hyperplastic nodule formation. It also promoted apoptosis and thereby eliminated
DEN-induced HCC in rats [127]. Yallapu et al. have also reported a curcumin-PLGA
nanoformulation (nano-CUR6) with enhanced cellular uptake in cisplatin-resistant
A2780CP ovarian and metastatic MDA-MB-231 breast cancer cells. The feasibility
of conjugating anticancer antibody [transferrin or anti-TAG-72 (CC49)] to the
nanoformulation was analyzed and CC49 antibody-coupled nanoparticles showed
intense localization in TAG-72-positive (HPAFII) cells compared to TAG72-negative (SKOV-3) cancer cells [128]. Curcumin and doxorubicin were
co-encapsulated in PLGA NPs and treated multidrug-resistant chronic myeloid
leukemia (CML) blast-like cancer cells (K-562 cells) more effectively. Initially,
expression of multidrug resistance protein 1 (MDR1) and Bcl-2 were downregulated
by curcumin and inhibited the nuclear efflux mechanism; the subsequent release
of doxorubicin stimulated cancer cell death [129].
Researchers have also focused on chitosan-based derivatives for formulating
nanoparticles for the delivery of curcumin. Curcumin-loaded dextran sulfatechitosan NPs (200–220 nm) showed preferential killing of cancer cells, thereby
sparing the normal cells. Figure 4 shows the cellular uptake of curcumin
encapsulated in dextran sulfate-chitosan NPs using fluorescent microscopy in
human breast adenocarcinoma (MCF-7), human prostate cancer (PC-3), and
human osteosarcoma (MG-63) cell lines and also in normal cells (L929). The cell
viability assay showed enhanced cancer cell death (MCF-7, 40.5%; MG 63, 34%;
PC3, 34%; and L929, 18%) and the ability of the nanoformulation to induce
apoptosis was confirmed in MCF-7 cells [130]. Anitha et al. have also loaded
curcumin onto water-soluble chitosan derivatives O-carboxymethyl chitosan
(O-CMC) and N,O-carboxymethyl chitosan (N,O-CMC). Curcumin-loaded
O-CMC and N,O-CMC NPs (15–200 nm) were found to be biocompatible and
induced apoptotic cancer cell death in MCF-7 and PC-3 in a very effective way,
thereby retaining its safety for normal cells [131, 132].
Das et al. reported a nanoformulation with a tripolymeric composite carrier
(alginate, chitosan and Pluronic) by ionotropic pre-gelation followed by
polycationic crosslinking for the delivery of curcumin to cancer cells. The IC 50
values for free curcumin and encapsulated curcumin on Hela cells were found to be
13.28 and 14.34 mM, respectively. The green fluorescence inside the Hela cells
visualized using fluorescent microscopy confirmed the cellular internalization of
curcumin-loaded composite NPs [133]. A simple nanoprecipitation method resulted
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S. Maya et al.
in cell proliferation (cyclin D1), invasion (MMP-9), and angiogenesis (VEGF)
was inhibited by the nanocurcumin. The study also demonstrated that the nanoformulation increased the half life of curcumin and made it more bioavailable
in vivo [126]. The effectiveness of curcumin encapsulated in PLGA NPs (NanoCurc)
against hepatocellular carcinoma (HCC) has been evaluated using a rat model
with oral diethylnitrosamine (DEN)-induced HCC. The study reported that this
nanocurcumin was more effective than free curcumin as a free-radical quencher
in combating the oxidative damage of hepatic cells and prevented DEN-induced
hyperplastic nodule formation. It also promoted apoptosis and thereby eliminated
DEN-induced HCC in rats [127]. Yallapu et al. have also reported a curcumin-PLGA
nanoformulation (nano-CUR6) with enhanced cellular uptake in cisplatin-resistant
A2780CP ovarian and metastatic MDA-MB-231 breast cancer cells. The feasibility
of conjugating anticancer antibody [transferrin or anti-TAG-72 (CC49)] to the
nanoformulation was analyzed and CC49 antibody-coupled nanoparticles showed
intense localization in TAG-72-positive (HPAFII) cells compared to TAG72-negative (SKOV-3) cancer cells [128]. Curcumin and doxorubicin were
co-encapsulated in PLGA NPs and treated multidrug-resistant chronic myeloid
leukemia (CML) blast-like cancer cells (K-562 cells) more effectively. Initially,
expression of multidrug resistance protein 1 (MDR1) and Bcl-2 were downregulated
by curcumin and inhibited the nuclear efflux mechanism; the subsequent release
of doxorubicin stimulated cancer cell death [129].
Researchers have also focused on chitosan-based derivatives for formulating
nanoparticles for the delivery of curcumin. Curcumin-loaded dextran sulfatechitosan NPs (200–220 nm) showed preferential killing of cancer cells, thereby
sparing the normal cells. Figure 4 shows the cellular uptake of curcumin
encapsulated in dextran sulfate-chitosan NPs using fluorescent microscopy in
human breast adenocarcinoma (MCF-7), human prostate cancer (PC-3), and
human osteosarcoma (MG-63) cell lines and also in normal cells (L929). The cell
viability assay showed enhanced cancer cell death (MCF-7, 40.5%; MG 63, 34%;
PC3, 34%; and L929, 18%) and the ability of the nanoformulation to induce
apoptosis was confirmed in MCF-7 cells [130]. Anitha et al. have also loaded
curcumin onto water-soluble chitosan derivatives O-carboxymethyl chitosan
(O-CMC) and N,O-carboxymethyl chitosan (N,O-CMC). Curcumin-loaded
O-CMC and N,O-CMC NPs (15–200 nm) were found to be biocompatible and
induced apoptotic cancer cell death in MCF-7 and PC-3 in a very effective way,
thereby retaining its safety for normal cells [131, 132].
Das et al. reported a nanoformulation with a tripolymeric composite carrier
(alginate, chitosan and Pluronic) by ionotropic pre-gelation followed by
polycationic crosslinking for the delivery of curcumin to cancer cells. The IC 50
values for free curcumin and encapsulated curcumin on Hela cells were found to be
13.28 and 14.34 mM, respectively. The green fluorescence inside the Hela cells
visualized using fluorescent microscopy confirmed the cellular internalization of
curcumin-loaded composite NPs [133]. A simple nanoprecipitation method resulted
218
S. Maya et al.