Nanocomplexes assembled from bioactive peptides, caseinophosphopeptides
(CPPs), and chitosan were used for the encapsulation of EGCG. EGCG-loaded
chitosan-CPP nanoparticles (150 nm) showed a dose-dependent cellular internalization inside human colon carcinoma (Caco-2) cell lines. Furthermore, the intestinal permeability of EGCG using a Caco-2 monolayer was enhanced significantly
as delivered by nanoparticles, which indicated the promising elevation of
EGCG bioavailability [155]. To address the issue of poor absorption followed
by the oral administration of EGCG, EGCG has been encapsulated in chitosantripolyphosphate nanoparticles and the oral absorption of EGCG evaluated in Swiss
Outbred mice. The study observed an enhanced exposure of EGCG to the jejunum,
resulting in increased plasma concentrations of EGC and suggesting that chitosan
NPs could be useful for enhancing oral delivery, and therapeutic application, of
EGCG in a number of disease conditions. [156].
EGCG encapsulated by poly(lactic acid)–poly(ethylene glycol) (PLA–PEG)
nanoparticles was evaluated against prostate cancer cells. They observed that
72% of apoptosis was induced in prostate cancer cell lines (PC-3) when treated
with 2.74 mmol/L nano-EGCG but only with 40 mmol/L of non-encapsulated
EGCG, indicating the ability of nano-EGCG to induce enhanced cancer cell death
with lower doses. Also, fibroblast growth factor (FGF)-induced angiogenesis was
more effectively inhibited with nano-EGCG (3 mg EGCG) than with free EGCG.
Thus, the study proved that PLA–PEG nanoparticles retained the biological effectiveness of EGCG with over tenfold dose advantage for exerting its proapoptotic
and angiogenesis inhibitory effects [157, 158]. Researchers tried to explore the
concept of nanochemoprevention using EGCG NPs functionalized with the small
targeting molecule prostate-specific membrane antigen (PSMA) that exhibits a
selective in vitro efficacy against PSMA-expressing prostate cancer cells.
PLGA–PEG–COOH was conjugated with a glutamate-containing urea-based inhibitor (DCL, which contains a primary amine that allows amide bond formation with
the carboxyl terminal groups of PEG monomer and has a high affinity for PSMA)
[159]. Singh et al. investigated the effect of EGCG and theaflavin loaded within
PLGA nanoparticles alone and in combination with the anticancer drug cisplatin in
several human cancer lines: A549 (lung carcinoma), HeLa (cervical carcinoma) and
THP-1 (acute monocytic leukemia). They showed that the nanoformulation in
combination with cisplatin exerted an enhanced anticancer potential by inhibiting
cell proliferation, metastasis, angiogenesis, and apoptosis biomarkers, resulting in a
20-fold dose advantage over the free drug [160]. Gelatin can act as a good carrier
for the natural polyphenols. EGCG was encased using a layer-by-layer (LbL)
technique into 200-nm sized gelatin nanoparticles consisting of a soft gel-like
interior with or without a surrounding LbL shell of polyelectrolytes (polystyrene
sulfonate/polyallylamine hydrochloride), polyglutamic acid/poly-L-lysine, dextran
sulfate/protamine sulfate, or carboxymethyl cellulose/gelatin. Nanoencapsulated
EGCG retained its biological activity and blocked hepatocyte growth factor
Phytomedicine-Loaded Polymeric Nanomedicines: Potential Cancer Therapeutics
227
(CPPs), and chitosan were used for the encapsulation of EGCG. EGCG-loaded
chitosan-CPP nanoparticles (150 nm) showed a dose-dependent cellular internalization inside human colon carcinoma (Caco-2) cell lines. Furthermore, the intestinal permeability of EGCG using a Caco-2 monolayer was enhanced significantly
as delivered by nanoparticles, which indicated the promising elevation of
EGCG bioavailability [155]. To address the issue of poor absorption followed
by the oral administration of EGCG, EGCG has been encapsulated in chitosantripolyphosphate nanoparticles and the oral absorption of EGCG evaluated in Swiss
Outbred mice. The study observed an enhanced exposure of EGCG to the jejunum,
resulting in increased plasma concentrations of EGC and suggesting that chitosan
NPs could be useful for enhancing oral delivery, and therapeutic application, of
EGCG in a number of disease conditions. [156].
EGCG encapsulated by poly(lactic acid)–poly(ethylene glycol) (PLA–PEG)
nanoparticles was evaluated against prostate cancer cells. They observed that
72% of apoptosis was induced in prostate cancer cell lines (PC-3) when treated
with 2.74 mmol/L nano-EGCG but only with 40 mmol/L of non-encapsulated
EGCG, indicating the ability of nano-EGCG to induce enhanced cancer cell death
with lower doses. Also, fibroblast growth factor (FGF)-induced angiogenesis was
more effectively inhibited with nano-EGCG (3 mg EGCG) than with free EGCG.
Thus, the study proved that PLA–PEG nanoparticles retained the biological effectiveness of EGCG with over tenfold dose advantage for exerting its proapoptotic
and angiogenesis inhibitory effects [157, 158]. Researchers tried to explore the
concept of nanochemoprevention using EGCG NPs functionalized with the small
targeting molecule prostate-specific membrane antigen (PSMA) that exhibits a
selective in vitro efficacy against PSMA-expressing prostate cancer cells.
PLGA–PEG–COOH was conjugated with a glutamate-containing urea-based inhibitor (DCL, which contains a primary amine that allows amide bond formation with
the carboxyl terminal groups of PEG monomer and has a high affinity for PSMA)
[159]. Singh et al. investigated the effect of EGCG and theaflavin loaded within
PLGA nanoparticles alone and in combination with the anticancer drug cisplatin in
several human cancer lines: A549 (lung carcinoma), HeLa (cervical carcinoma) and
THP-1 (acute monocytic leukemia). They showed that the nanoformulation in
combination with cisplatin exerted an enhanced anticancer potential by inhibiting
cell proliferation, metastasis, angiogenesis, and apoptosis biomarkers, resulting in a
20-fold dose advantage over the free drug [160]. Gelatin can act as a good carrier
for the natural polyphenols. EGCG was encased using a layer-by-layer (LbL)
technique into 200-nm sized gelatin nanoparticles consisting of a soft gel-like
interior with or without a surrounding LbL shell of polyelectrolytes (polystyrene
sulfonate/polyallylamine hydrochloride), polyglutamic acid/poly-L-lysine, dextran
sulfate/protamine sulfate, or carboxymethyl cellulose/gelatin. Nanoencapsulated
EGCG retained its biological activity and blocked hepatocyte growth factor
Phytomedicine-Loaded Polymeric Nanomedicines: Potential Cancer Therapeutics
227