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8/10/2019 Synthesis of PLGA Nanoparticles of Tea Polyphenols and Their Strong in Vivo Protective Effect Against Chemically I
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International Journal of Nanomedicine Dovepressopen access to scientific and medical research
Open Access Full Text Article O r i g i n a l R e s e a r c h
Synthesis of PLGA nanoparticles of
tea polyphenols and their strong invivo protective eect againstchemically induced !A damage
This article "as pu#lished in the follo"ing ove Press $ournal%
&nternational 'ournal of
!anomedicine () April *+()
!um#er of times this article has #een vie"ed
Amit ,umar Srivastava(
Priyan-a .hatnagar*
/adhuli-a Singh(
San$ay /ishra(
Pradeep ,umar*
0ogesh"er Shu-la(
,ailash 1hand Gupta(2*
(Proteomics La#oratory2 &ndian&nstitute of Toxicology Research
31S&R42 Luc-no"2 &ndia5 *!ucleic AcidResearch La#oratory2 &nstitute ofGenomics and &ntegrative .iology31S&R42 elhi 6niversity 1ampus2 &ndia
Abstract: In
spite of proficient
results of severalphytochemicals in
preclinical
settings, the
conversion rate
from bench to
bedside is not very
encouraging.
Many reasons are
attributed to this
limited success,
including
inefficient
systemic delivery
and bioavailability
under in vivo
conditions. To
achieve improved
efficacy,
polyphenolic
constituents of
black (theaflavin
[TF] and green
(epigallocatechin!
"!gallate [#$%$]
tea in poly(lactide!
co!glycolide
nanoparticles
(&'$!)&s *ere
entrapped *ith
entrapment efficacy of 7+- and /-,
respectively. Further, their preventive potential
against 0,+!dimethylben1anthracene (2M3!induced 2) damage in mouse skin using
2) alkaline un*inding assay *as evaluated.
&retreatment (topically of mouse skin *ith
either TF or #$%$ (+44 g5mouse doses
e6hibits protection of 78."7- and ."-,
respectively, against 2M3!induced 2)
damage. 9o*ever, pretreatment *ith TF!loaded
&'$!)&s protects against 2) damage
/7.7+- by +54th dose of bulk, 0+.0:- by
+5+4th dose of bulk, and 0.7/- by +58th dose
of bulk. ;imilarly, 8+.- (+54th of bulk,
80./"- (+5+4th of bulk, and /".+7- (+58th of
bulk prevention *as noted using #$%$!loaded
&'$!)& doses. These results sho*ed that tea
polyphenol!loaded &'$!)&s have 7"4!fold
dose!advantage than bulk TF or #$%$ doses.
dditionally, TF! or #$%$!loaded &'$!)&s
sho*ed significant potential for induction of
2) repair genes (XRCC1, XRCC3, and
ERCC3 and suppression of 2) damage
responsive genes (p53, p21, MDM2,
GADD45, and COX-2 as compared *ith
respective bulk TF or #$%$ doses. Taken
together, TF! or #$%$!loaded &'$!)&s
sho*ed a superior ability to prevent 2M3!
induced 2) damage at much lo*er
concentrations, thus opening a ne* dimension
in chemoprevention research.
Keywords: 2) alkaline un*indingassay, mouse skin, 2) repair
1orrespon
dence%
0ogesh"er
Shu-laProteomic
s
La#oratory2 &ndian &nstitute
of Toxicology Research
31S&R42
PO .ox 8+2 /G/arg2 Luc-no"6P **9++(2 &ndia
Tel +:( ;**
*:9)8*84 has gained
importance for the encapsulation of a *ide variety of drugs as it
is biodegradable, biocompatible, capable of controlling the
release of the incorporated entity, and less to6ic.+/,+0
The choice
of &'$ *as also supported by the fact that it can be used to
form stable nanoparticles ()&s, and has already been approved
for use in humans by the B; Food and 2rug dministration.+
Thus, it has been chosen as the polymer scaffold to fabricate
the )&s used in the present study.
Mammalian skin forms a
hurdle bet*een the host and
surrounding
environments.+:,4
9o*ever,
it is also a ma=or route of
entry for several to6ic agents
and a potential target of
environmental ha1ards, *hich
can cause several skin!related
abnormalities including skin
cancer.+
#pidemiological
stud!ies suggest that almost
one!third of all ne* cancers
diagnosed annually
*orld*ide originate from
skin.
;everal studies sho*
an association bet*een
different human cancers and
lifestyle5dietary habitsA
additionally, detailed studiesof muta!tional events in
human cancers have provided
evidence for a direct
involvement of
environmental
mutagens5carcinogens in the
progression of different types
of cancer.",7
In the present study, a
&'$!based drug
development strategy *asfollo*ed to encapsulate TF
and #$%$. The authors
envisioned that )&s!
mediated delivery of
bioactive catechins from
black tea (TF and green tea
(#$%$ could be useful in
enhancing their protective
potential against 0,+!
dimethylben1[a]anthracene
(2M3!induced 2)damage in mouse skin
tissue.
&ateria's andmethods1hemicals&'$ 84>84 (molecular *eight
[MC] 74D08 k2a, polyvinyl
alcohol (MC "4 k2a, #$%$,
TF, and 2M3 *ere purchased
from ;igma!ldrich (;t 'ouis,
M?, B;. 9ydro6ylapatite
and ),)!dimethylformamide
*ere purchased from ;isco
Eesearch 'aboratory (Mumbai,
India. ll other chemicals
used *ere of analytical grade
purity and procured locally.
Formulationof TFE or=G1GEloadedPLGAE!PsTF! or #$%$!loaded &'$!
)&s *ere prepared using the
standard solvent evaporation
method,8
*ith minor
modifications. 3riefly, a 4.8m' a
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Dovepress Protection against !A damage #y nanotied tea polyphenols
by *ashing *ith *ater, and finally, the )&s *ere free1e!dried
*ith a Bnivapo +849 Bnicryo free1e dryer (Bnie
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The mean particle si1e and distribution, as *ell as the
=valuation of TF or =G1Grelease
1eta potential of the TF! or #$%$!loaded &'$!)&s *as from !Psdetermined by a dynamic light scattering techni
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Dovepress Protection against !A damage #y nanotied tea polyphenols
,ab'e 1 1haracteristics of TFJ=G1G loadedE!Ps
"anopartic'es - ie'd #i)e nm eta potentia' rug 3oading ncapsu'ation
+I m - 6ciency -
=G1GEPLGA :9?:+ (*
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9igure 1 Particle sie distri#ution of epigallocatechinE)Egallate 3A4 andtheaMavin4nanoparticles? 3
"ote: Nalues are represented as meanstandard deviation?
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8/10/2019 Synthesis of PLGA Nanoparticles of Tea Polyphenols and Their Strong in Vivo Protective Effect Against Chemically I
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having all the properties re
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8/10/2019 Synthesis of PLGA Nanoparticles of Tea Polyphenols and Their Strong in Vivo Protective Effect Against Chemically I
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Dovepress Protection against !A damage #y nanotied tea polyphenols
A 100 EGCG PLGA NPs90
80
release 70
60
50
%d
rug
40
30
20
100
0 1 2 3 4 5 6 7 8 9 10
Numer !" days
B #0 $% PLGA NPs80
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60
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40
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9igure % lnEvitro releaseA4and TFprole34PLGAE!Ps?of =G1G 3
"ote: Nalues are represented as meanstandard deviation?
Abbre7iations: =G1G2epigallocatechinE)Egallate5 PLGAE!P2 poly3lactideEcoEglycolide4 nan
time interval of 7 hours follo*ing the doses of TF or #$%$. ;ignificant
protection (78."7- *as observed at the dose of +44 g5mouse of bulk TF
in 7 hours (Figure 8, *hile TF!loaded &'$!)&s at doses 8, +4, and 4g5mouse provided protection of /7.74-, 0+.+:-, and 0.7/-,
respectively, *hich clearly sho*s about a "4!fold dose!advantage over
the bulk counterpart. ;imilarly,
*ith bulk #$%$ (+44 g5
mouse, .- protection *as
observed, *hile #$%$!loaded
&'$!)&s at 8, +4, and 4
g5mouse dose provided
8+.-, 80./"-, an
protection, res
sho*ing about a "!f
advantage over bulk
9o*ever, &'$!lo
($roup KI and #$%$
25
rea(s
20
s
trand
15
!"
10
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0
II
9igure 4 Reduction in /.AEinduced strand #rea-s#y #ul- and poly3lactideEcoEglycolide4Eloaded teapolyphenols?
"otes: ata sho"n is the meanstandard deviationof all the animals5
indicatesP,+?+;5Qindicatessignifigniccantrof nanotied teapolyphenol over its#ul-2 P,+?+;?
Abbre7iation:/.A2
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