European Journal of Pharmaceutical Sciences 44 (2011) 422–426

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European Journal of Pharmaceutical Sciences

journal homepage: www.elsevier.com/locate/ejps

Chitosan nanoparticles enhance the plasma exposure of ( )-epigallocatechin

gallate in mice through an enhancement in intestinal stability
Admire Dube, Joseph A. Nicolazzo, Ian Larson ⇑
Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University (Parkville Campus), 381 Royal Parade, Parkville, Victoria 3052, Australia

a r t i c l e i n f o a b s t r a c t

Article history: The green tea catechin ( )-epigallocatechin gallate (EGCG) has attracted significant research interest due
Received 31 May 2011 to its beneficial therapeutic effects, which include anti-oxidant, neuro-protective and anti-cancer effects.
Received in revised form 24 August 2011 However, the therapeutic potential of EGCG following oral consumption is limited by its poor absorption.
Accepted 5 September 2011
To address this issue, EGCG has been encapsulated in chitosan-tripolyphosphate nanoparticles (CS NPs)
Available online 8 September 2011
and the oral absorption of EGCG evaluated in Swiss Outbred mice. Administration of the CS NPs enhanced
the plasma exposure of total EGCG by a factor of 1.5 relative to an EGCG solution, with plasma AUC(0 5 h)
Keywords:
values of 116.4 ± 4.1 and 179.3 ± 10.8 nM.h (mean ± s.d., n = 3 5) for the EGCG solution and CS NPs,
( )-Epigallocatechin gallate (EGCG)
Oral absorption
respectively. Associated with the increased plasma exposure of EGCG was an enhancement in concentra-
Plasma exposure tions of EGCG in the stomach and jejunum of mice following CS NP administration. A 2.3-fold increase in
Chitosan-tripolyphosphate nanoparticles the apparent exposure of EGCG to the jejunum (AUCj) was observed following CS NP encapsulation, with
(CS NPs) AUCj(0 5 h) values of 5.3 ± 1.1 and 12.3 ± 1.5 lM.h (mean ± s.d., n = 3 5) for the EGCG solution and CS
Intestinal stability NPs, respectively. The enhanced exposure of EGCG to the jejunum was likely responsible for the increased
plasma concentrations of EGCG. The findings from this study suggest that CS NPs may be a useful
approach for enhancing oral delivery, and therapeutic application, of EGCG in a number of disease
conditions.
Ó 2011 Published by Elsevier B.V.

1. Introduction However, following oral administration of EGCG to rodents at rel-

( )-Epigallocatechin gallate (EGCG) (Fig. 1), a flavonoid belong-
ing to the catechin class, is found in various foods and beverages,
particularly in green tea, where it is present in high amounts
(Wang et al., 2000; Hackman et al., 2008). Recently, EGCG has
attracted research interest as several in vitro and animal studies
have demonstrated that it possesses favourable therapeutic effects,
which include anti-oxidant, anti-viral, anti-inflammatory, cardio-
protective, neuro-protective and anti-cancer effects (Lambert and
Yang, 2003; Nagle et al., 2006; Zaveri, 2006; Kuzuhara et al.,
2008; Ho et al., 2009; Luo et al., 2010).
However, the therapeutic potential of EGCG is limited by its
poor systemic absorption following oral consumption (Chen
et al., 1997; Lambert et al., 2003; Williamson, 2005; Lin et al.,
2007; Huo et al., 2008). Studies indicate that, at most, 5% of an
EGCG dose is absorbed into the systemic circulation of rats follow-
ing oral administration (Chen et al., 1997; Zhu et al., 2000; Lin
et al., 2007). It has been estimated that in order for EGCG to induce
relevant therapeutic effects, a concentration of at least 10 lM is
required (Scalbert and Williamson, 2000; Yang et al., 2008).
⇑ Corresponding author. Tel.: +61 3 99039570; fax: +61 3 99039583.
E-mail address: ian.larson@monash.edu (I. Larson).
evant doses, peak plasma concentrations in the nM range are ob-
tained (Chen et al., 1997; Lin et al., 2007; Dube et al., 2011), and
with even higher doses (equivalent to ingestion of multiple cups
of tea), plasma concentrations of EGCG are at most 1 lM (Balentine
et al., 1997; Raneva et al., 2005; Lambert et al., 2006a). The low oral
absorption of EGCG, and that of catechins in general, has mainly
been attributed to poor stability within the gastro-intestinal tract
(GIT) and poor permeability across the intestine (Zhu et al., 2000;
Cai et al., 2002; Chow et al., 2005; Lambert et al., 2006b; Huo
et al., 2008; Wang et al., 2009). Catechins are unstable in gastro-
intestinal solutions (Zhu et al., 1997; Huo et al., 2008), and as we
demonstrated recently, approximately 80% of EGCG degrades in
simulated intestinal fluid pH 7.4 (37 °C) over a 1 h period (Dube
et al., 2010a). In addition to inherent instability, the apparent per-
meability co-efficient (Papp) of EGCG across Caco-2 cells has been
reported to be 0.83  10 7 cm/s (Zhang et al., 2004), suggesting
very low permeability, as the Papp for the poorly-permeable marker
mannitol is at least 6.8  10 6 cm/s (Polentarutti et al., 1999; Ste-
phens et al., 2002; Yang et al., 2003).
In order to fully maximise the therapeutic utility of EGCG, there
is a need to enhance its oral absorption (Huo et al., 2008; Schee-
pens et al., 2009). Previous strategies to enhance the oral absorp-
tion of EGCG have included the formulation of a peracetate ester

0928-0987/$ - see front matter Ó 2011 Published by Elsevier B.V.

doi:10.1016/j.ejps.2011.09.004
 A. Dube et al. / European Journal of Pharmaceutical Sciences 44 (2011) 422–426
Fig. 1. Chemical structure of EGCG.
pro-drug of EGCG, which is more stable than EGCG in solution
(Lam et al., 2004). Oral administration of peracetylated EGCG to
mice resulted in a 2.4-fold increase in the plasma exposure of
EGCG, relative to an EGCG solution (Lambert et al., 2006b). Another
approach has been the co-administration of EGCG with the com-
pounds piperine or genistein. Piperine and genistein are able to in-
hibit the biotransformation and the intestinal efflux of EGCG,
respectively (Lambert et al., 2004, 2008). With the use of these
compounds, the plasma exposure of EGCG could be increased up
to 1.5-fold (Lambert et al., 2004, 2008). However, the use of pro-
drugs or co-administration of metabolism or efflux inhibitors
may not be the most appropriate approaches due to possible tox-
icity arising from these compounds, or the impact of these agents
on the oral absorption of toxins normally denied access by these
metabolizing enzymes or efflux transporters.
Our approach to overcome the issue of poor oral bioavailability
has been to encapsulate EGCG in chitosan nanoparticle (CS NP)
delivery systems. Previously, we reported that encapsulation in
CS NPs increases the stability of EGCG in simulated GIT fluids,
and leads to enhanced absorption of EGCG in an in vitro mouse
intestinal permeability model (Dube et al., 2010a,b). Our investiga-
tions suggested that the enhanced absorption of EGCG was exerted
by enhanced stability imparted by the NPs on EGCG, leading to in-
creased flux of EGCG across the intestine (Dube et al., 2010b). How-
ever, the impact of the CS NPs on the oral absorption of EGCG
in vivo remains unknown. Therefore, the aim of the present study
was to determine the impact of encapsulation of EGCG in CS NPs
on the plasma exposure of EGCG following administration to mice.
In addition, this study investigates whether any enhancement in
plasma exposure induced by the NPs is related to increased stabil-
ity of EGCG in the GIT, as has been suggested from in vitro studies.
2. Materials and methods
2.1. Chemicals
EGCG (95% purity), ascorbic acid (AA), tris(2-carboxyethyl)
phosphine (TCEP) and disodium-ethylenediaminetetraacetic acid
(Na2EDTA) were obtained from Sigma–Aldrich Co (St Louis, MO).
The enzymes b-D-glucuronidase (G-7896, EC 3.2.1.31, from Esche-
richia coli with 9  106 U/g solid) and sulfatase (S-9754, EC 3.1.6.1,
from Abalone entrails with 2.3  105 U/g solid) were also obtained
from Sigma Aldrich Co (St Louis, MO). Stock solutions of these
enzymes were prepared in 50 mM K2HPO4 buffer and stored at
20 °C until required. Acetic acid (glacial) was obtained from Ajax
Finechem (Taren Point, Australia) and HPLC grade acetonitrile was
purchased from Merck (Darmstadt, Germany). All other chemicals
and solvents were of analytical grade and were used as received.
423
De-ionised water was obtained from a MilliporeÒ filtration system
(Billerica, MA).
2.2. Encapsulation of EGCG in CS NPs
CS NPs encapsulating EGCG were prepared as previously de-
scribed (Dube et al., 2010b). Briefly, NPs were prepared by the
drop-wise addition of a tripolyphosphate (TPP) solution (0.1%, w/
v; pH 3) to a CS solution (0.1% w/v in 0.175% v/v acetic acid; pH
3) containing EGCG (0.05% w/v), under magnetic stirring for
10 min (700 rpm) at ambient temperature. NPs were collected by
centrifugation at 40,000g for 30 min and freeze-dried (Virtis
AdVantage™, USA) at 80 °C for 16 h. The CS NPs contained
3.7 ± 0.1 lg/mg of EGCG with an average size and zeta potential
of 440 ± 37 nm and 25 ± 1 mV, respectively, determined in Krebs
Bicarbonate-buffered Ringers solution pH 6.0 (Dube et al., 2010b).
2.3. Dosing of mice and sample collection
All animal experiments were approved by the Monash Institute
of Pharmaceutical Sciences Animal Ethics Committee and were
performed in accordance with the Australian National Health and
Medical Research Council guidelines for the care and use of ani-
mals for scientific purposes. Male Swiss Outbred mice (25–30 g)
were obtained from Monash Animal Services and were kept in
air-conditioned quarters with a room temperature of 20 ± 2 °C, rel-
ative humidity of 50 ± 10% and an alternating 12 h light: dark cycle.
Mice were fasted for 16 h prior to administration of the EGCG for-
mulations. To assess the plasma exposure of EGCG from solution, a
volume of an EGCG solution (0.11 mg/ml in 0.1 M HCl) was admin-
istered to mice by oral gavage equating to an EGCG dose of
0.76 mg/kg (Dube et al., 2011). To assess the plasma exposure of
EGCG from the CS NPs, a suspension of the NPs (35 mg/ml in
0.1 M HCl) was prepared. The NPs were suspended in 0.1 M HCl
through sonication for 30 s and immediately thereafter, a volume
of the suspension administered by oral gavage to mice to give an
equivalent dose of 0.76 mg/kg EGCG. At pre-determined time
intervals post-dose (30, 60, 90, 150, 210, 300 and 360 min), mice
(n = 3 5 at each time point) were anaesthetized with an intra-
peritoneal dose of ketamine (133 mg/kg) and xylazine (10 mg/
kg), and blood collected by cardiac puncture into polyethylene
tubes containing 10 ll of the anticoagulant heparin. Blood was
centrifuged at 16 000g for 5 min and 100 ll aliquots of plasma
(n = 2) collected into polyethylene tubes containing 20 ll of
20 mM AA and 13 mM TCEP stabilizing solution, which we have
previously reported as an effective stabilizer of EGCG in aqueous
and plasma samples (Dube et al., 2010a,b). Plasma samples were
snap frozen using carbon-dioxide dry ice and stored at 20 °C until
HPLC analysis. The rationale for collecting two aliquots of plasma
for each sample was to allow for determination of both un-conju-
gated EGCG (i.e. non-metabolized EGCG) and total EGCG (i.e. the
sum of non-metabolized, and glucuronidated and sulfated EGCG).
On the day of the assay, EGCG was extracted from the plasma sam-
ples and quantified as described previously (Dube et al., 2011).
Briefly, to determine total EGCG, 5 ll of b-glucuronidase
(500,000 U/ml) and 5 ll of sulfatase (4000 U/ml) enzymes were
added to the plasma sample and incubated at 37 °C for 45 min.
To determine un-conjugated EGCG, 10 ll of K2HPO4 buffer were
added in place of the enzymes, and the sample also incubated for
45 min. After incubation, EGCG was extracted from the samples
using ethyl acetate. The ethyl acetate layer containing EGCG was
separated from the sample, evaporated, and the residue reconsti-
tuted with 100 ll of 15% v/v aqueous acetonitrile solution. A
50 ll aliquot of this solution was injected onto the HPLC column
and EGCG was quantified using a validated HPLC/UV method de-
scribed previously (Dube et al., 2011).
424 A. Dube et al. / European Journal of Pharmaceutical Sciences 44 (2011) 422–426

Table 1
Plasma pharmacokinetic parameters of EGCG (un-conjugated and total) following oral administration of an EGCG solution and CS NPs to Swiss Outbred mice at a dose of 0.76 mg/
kg.

Parameter EGCG solution CS NP

Un-conjugated Total Un-conjugated Total
AUC(0 5 h) (nM.h) 114.3 ± 4.1⁄ 116.4 ± 4.1⁄⁄ 166.0 ± 12.0⁄ 179.3 ± 10.8⁄⁄
Cmax (nM) 31.5 ± 3.3 34.3 ± 2.0 35.1 ± 9.2 37.8 ± 6.8
Tmax (h) 1.5 1.5 1.5 1.5

Data shown are the mean ± s.d. from 3–5 animals. Statistically significant differences in the plasma exposure between the EGCG solution and the CS NPs are indicated by ⁄ for
unconjugated EGCG and ⁄⁄ for total EGCG, respectively (z > 1.96).

2.3.1. Assessment of the impact of the CS NPs on the stability of EGCG
in the GIT of the mice
To evaluate whether encapsulation in CS NPs was associated
with enhanced stability of EGCG within the GIT of mice, the con-
centration of EGCG in the stomach and jejunum of dosed mice
was determined. Following administration of the EGCG solution
or the CS NPs (as described in Section 2.3.1), samples were ob-
tained from mice sacrificed at the 90, 150 and 300 min time points
(n = 3 5 at each time point). To obtain gastric samples, the stom-
ach was isolated and an incision made along the midline, exposing
the inner contents of the stomach. Using a flat metal spatula, the
contents of the stomach were thoroughly scraped and collected
into polyethylene tubes containing 1 ml of 20 mM AA and 13 mM
TCEP stabilizing solution. To obtain jejunal samples, the jejunum
(i.e. the segment beginning 5 cm distal to the ligament of Treitz
and extending distally for 10 cm (Stephens et al., 2002)), was re-
moved and using a syringe, flushed thoroughly with 20 mM AA
and 13 mM TCEP stabilizing solution into a polyethylene tube.
Samples were vortexed for 1 min before being filtered through a
0.1 lm filter and a 50 ll aliquot of the filtrate kept for assay. EGCG
that was free in solution, i.e. not encapsulated in the NPs, was as-
sayed according the validated HPLC/UV method (Dube et al.,
2010a).
2.4. Data analysis
Statistical differences between the various experimental treat-
ments were determined using the independent samples student’s
t test or the analysis of variance (ANOVA) test using SPSS Statistics
v17.0 software (Chicago, IL). Values of p < 0.05 indicated statisti-
cally significant differences. The plasma exposure of EGCG follow-
ing administration of the EGCG solution and the CS NPs was
determined through calculation of the area under the plasma con-
centration versus time curve from time zero to 5 h post-dose
(AUC0 5 h) using Bailer’s method (Bailer, 1988). Statistical differ-
ences between the AUC of un-conjugated or total EGCG were deter-
mined using the statistical z test, where z values greater than 1.96
indicated statistically significant differences (Bailer, 1988; Yuan,
1993; Nedelman et al., 1995). The peak plasma concentration
(Cmax) and time of peak concentration (Tmax) were obtained di-
rectly from the plasma concentration vs time profiles.
significant differences (p > 0.05) between the concentrations of
un-conjugated and total EGCG in the plasma samples were ob-
served, suggesting that minimal metabolism of EGCG occurred in
mice, as has previously been reported (Meng et al., 2002). The en-
hanced plasma exposure of EGCG through the use of CS NPs may
provide some benefit for the treatment of systemic disorders
where EGCG is suggested to exert therapeutic activity, albeit fur-
ther studies may be required to obtain plasma concentrations clo-
ser to therapeutically-active concentrations.
Fig. 2 shows the plasma concentration versus time profile of
EGCG obtained following administration of the EGCG solution
and the CS NPs to mice. It was observed that administration of
the EGCG solution resulted in plasma concentrations which peaked
at approximately 1.5 h and after this period declined to signifi-
cantly lower levels (i.e. p < 0.05 for plasma concentrations between
1.5 and 5 h). However, following administration of the CS NPs,
plasma concentrations of EGCG peaked at approximately 1.5 h
and were sustained up to 5 h (i.e. p > 0.05 for plasma concentra-
tions between 1.5 and 5 h). At the 1.5 h time point, plasma concen-
trations of EGCG were not significantly different between
administration of the EGCG solution and the CS NPs (Table 1). This
suggested that the CS NPs may not have enhanced the plasma
exposure of EGCG through increasing the permeability of EGCG
but rather through providing sustained concentrations of EGCG
in the GIT for subsequent availability in the plasma. Such a ratio-
nale was inferred as it was anticipated that an increase in intestinal
permeability would lead to an increase in the peak plasma concen-
trations of EGCG and/or a decrease in the time to reach peak plas-
ma concentrations (Damgé et al., 2007; Sarmento et al., 2007). As
the CS NPs had a mean size of 440 ± 37 nm, it was unlikely that
the particles could have enhanced the plasma exposure by being

2.5. Results and discussion

2.5.1. Plasma exposure of EGCG and impact of CS NP encapsulation

The plasma exposure of EGCG in mice was determined follow-
ing oral administration of the EGCG solution and the CS NPs and
the associated pharmacokinetic parameters for EGCG are listed in
Table 1.
Administration of the CS NPs resulted in a significantly en- Fig. 2. Plasma concentrations of total EGCG after oral administration of an EGCG
solution (-d-) and CS NP formulation (-s-) to Swiss Outbred mice (0.76 mg/kg).
hanced plasma exposure (AUC(0 5 h)) of both un-conjugated and Data shown are the mean ± s.e.m. from 3–5 animals. For clarity, profiles of total
total EGCG, relative to the EGCG solution (z > 1.96), with the CS EGCG only are shown as there was no significant difference (p < 0.05) between the
NPs leading to a 1.5-fold higher plasma exposure. No statistically plasma concentrations of un-conjugated and total EGCG.
 A. Dube et al. / European Journal of Pharmaceutical Sciences 44 (2011) 422–426
Fig. 3. Concentrations of EGCG measured in samples obtained from the stomach and jejunum of Swiss Outbred mice following oral administration of the EGCG solution
( ) and the CS NPs formulation ( ). In both treatments, the dose of EGCG administered to mice was 0.76 mg/kg. Data are the mean ± s.e.m. from 3–5 animals.
⁄
Indicates statistical differences in concentration between administration of the EGCG solution and the CS NPs.
taken up across the intestinal wall through the process of transcy-
tosis. This is because only particles with a mean size under 100 nm
and particularly those approaching 50 nm, have the potential to be
taken up by intestinal cells (Florence et al., 1995; Florence and
Hussain, 2001; Barratt, 2003). In addition, we reported that these
CS NPs were unable to enhance the paracellular or passive
transcellular transport of compounds across the intestinal tissue
of mice (Dube et al., 2010b), and therefore it was unlikely that
the enhanced plasma exposure of EGCG with CS NP was due to
increased intestinal permeability. Rather, the enhancement in the
plasma exposure of EGCG was likely to be due to other effects of
the CS NPs, such as an enhancement in the stability of EGCG within
the GIT leading to increased flux across the intestine, as we have
previously reported from in vitro studies (Dube et al., 2010b). To
determine whether the CS NPs also enhanced the stability of EGCG
in vivo, the concentrations of EGCG in the GIT of the mice were also
determined.
2.5.2. Assessment of the impact of CS NPs on the stability of EGCG in
the stomach and jejunum of mice
Concentrations of EGCG in samples collected from the stomach
and jejunum of mice following oral administration of the EGCG
solution and the CS NPs were determined. Fig. 3 shows the concen-
trations of EGCG at 1.5, 2.5 and 5 h post dose. It should be noted
that the EGCG concentrations measured were reflective of concen-
trations in the sample of AA/TCEP solution, and were not the actual
concentrations of EGCG present in the gut segments. However, gi-
ven that samples from both the EGCG solution and CS NP-treated
mice were treated in an identical manner, any concentration differ-
ences observed were reflective of the in vivo situation.
It was observed that at 1.5 and 2.5 h following administration of
the CS NPs, EGCG gastric concentrations were significantly higher
than those detected following administration of the EGCG solution
(p < 0.05), whereas after 5 h, the concentrations were similar
(p > 0.05). In the jejunum, EGCG concentrations at the 2.5 h time
point were significantly higher following administration of the CS
NPs compared to the EGCG solution (p < 0.05), whereas at 1.5
and 5 h, the concentrations were similar (p > 0.05). These observa-
tions suggested that encapsulation of EGCG in CS NPs enhanced its
stability in the GIT of mice (in vivo), as we have previously
observed in vitro (Dube et al., 2010a,b). In-vivo, the stabilization
occurs firstly in the stomach and later in the jejunum as the CS
NPs require time to move from the stomach into the small intes-
tine and to release EGCG. By 5 h, it is likely that the CS NPs have
425
completely released EGCG (un-published data) and hence, the ef-
fect of the CS NPs on the stabilization of EGCG in the jejunum
dissipates.
It is possible that delayed gastric emptying following adminis-
tration of the CS NPs could have contributed to the enhanced con-
centrations of EGCG. To determine the impact of gastric emptying,
an assessment of the relative concentrations of EGCG in the stom-
ach samples to those in the jejunum samples, after administration
of the EGCG solution or the CS NPs was conducted (Table 2).
No significant difference (p > 0.05) in the stomach: jejunum
EGCG concentration ratios at each time point following adminis-
tration of the EGCG solution or the CS NPs was observed. It was ex-
pected that had delayed gastric emptying occurred, the ratio of the
stomach: jejunum EGCG concentrations following administration
of the CS NPs would have been significantly higher than observed
following administration of the EGCG solution, due to the accumu-
lation of EGCG in the stomach. Therefore, the results suggested that
delayed gastric emptying could be excluded as a factor enhancing
the gastro-intestinal concentrations of EGCG.
The jejunum has been reported as the main site of absorption
for flavonoid compounds (Matuschek et al., 2006). Consequently,
the ‘apparent’ exposure of the jejunal contents to EGCG was deter-
mined, through calculation of the area under the jejunal concentra-
tion vs time profiles (AUCj(0 5 h)). AUCj(0 5 h) was calculated
using Bailers approach as described in Section 2.4. AUCj(0 5 h)
was 5.3 ± 1.1 and 12.3 ± 1.5 lM.h (mean ± s.d., n = 3–5) following
administration of the EGCG solution and the CS NPs, respectively,
indicating that administration of the CS NPs had resulted in a
2.3-fold increase in the ‘apparent’ exposure of the jejunum to EGCG
over the 5 h period. The enhanced exposure of the jejunum to
EGCG was likely responsible for the enhancement in the plasma
exposure of EGCG, and was in agreement with the findings from
previous in vitro absorption studies, where significantly higher
Table 2
The ratios of the concentrations of EGCG measured in the stomach samples to those
measured in the jejunum samples at each of the sampling time points, following oral
administration of the EGCG solution or the CS NPs to Swiss Outbred mice. Data shown
are mean ratios ± (s.d.) (i.e. x: 1), calculated from 3–5 animals.
Time (min) EGCG solution CS NPs
Mean ratio (stomach: jejunum)
90 2.0 ± 0.1 4.9 ± 2.9
150 1.2 ± 0.9 1.3 ± 0.7
300 0.9 ± 0.1 0.9 ± 0.2
426 A. Dube et al. / European Journal of Pharmaceutical Sciences 44 (2011) 422–426
concentrations of EGCG were present on the mucosal side of the
jejunum following encapsulation in CS NPs (Dube et al., 2010b).
The enhanced exposure of the jejunum to EGCG following admin-
istration of the CS NPs could be potentially beneficial for inflamma-
tory conditions of the intestine such as Crohn’s disease, where
prolonged exposure to high concentrations of antioxidants such
as EGCG is required (Chapple, 1997; Porath et al., 2005). In addi-
tion, other locally and systemically-acting therapeutic compounds
which exhibit poor stability could be encapsulated in CS NPs to
enhance their stability and consequently, their therapeutic effec-
tiveness either in the GIT or in the systemic circulation.
3. Conclusion
Oral administration of EGCG encapsulated in CS NPs resulted in
a significant enhancement in the plasma exposure of EGCG relative
to an EGCG solution. The enhancement in oral absorption was
attributed to an increased exposure of EGCG to the jejunum due
to the stability enhancing effect of the CS NPs. CS NPs may there-
fore enable the future therapeutic application of EGCG in a number
of disease conditions.
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