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Gold Nanoparticle Conjugated PLGA-PEG-SA-PEG-PLGA Multiblock
Copolymer Nanoparticles: Synthesis, Characterization, In-vivo Release of
Rifampicin
Mani Gajendiran,a Sheik Mohammed Jainuddin Yousuf,b Vellaichamy Elangovan,b
Sengottuvelan Balasubramaniana, *
aDepartment of Inorganic Chemistry, Guindy Campus, University of Madras, Chennai, India –
600025.
bDepartment of Biochemistry, Guindy Campus, University of Madras, Chennai, India–600025.
*Corresponding author: E-mail - [email protected]
Supplementary Material
Electronic Supplementary Material (ESI) for Journal of Materials Chemistry BThis journal is © The Royal Society of Chemistry 2013
1. G
T
dendron
addition
spectral
surface
that AuN
stabilize
CPEG i
Fig. S1
Green synt
The reducti
n at pH 8.5
n of CPEG
analysis an
plasmon re
uNPs are un
ed AuNPs a
s given belo
1. (a) UV-vi
thesis of CP
on of Au (I
. It was ver
dendron at
nd the result
esonance (S
niformly arr
are about 17
ow.
isible spectr
PEG stabiliz
III) to Au (0
ry interestin
t 80 °C. Th
t is shown i
SPR) absorp
ranged on th
7 nm with s
rum and (b)
zed AuNPs
0) is facilita
ng to monit
he synthesiz
in the Fig.S
ption at 530
he CPEG p
spherical sh
) TEM imag
nm).
s
ated by citric
tor the rapi
zed AuNPs
1a. The AuN
0 nm. The T
polymer mat
hape. The sc
ges of CPEG
c acid units
id formation
were exam
NPs colloid
TEM image
trix and con
cheme of Au
G stabilized
present in t
n of AuNPs
mined by U
dal solution
es in Fig.S1
nfirm that t
uNPs synth
AuNPs (sca
the CPEG
s with the
UV-Visible
shows the
b indicate
the CPEG
hesis using
ale bar 20
Electronic Supplementary Material (ESI) for Journal of Materials Chemistry BThis journal is © The Royal Society of Chemistry 2013
O OO
O O
O O
OOHO
O O
OOH
OO
O
Au
Cl Cl
Cl Cl
+
1. pH 8.5
2. 80 °C
3. - Cl
O OO
O O
O O
OOHO
O O Au
Cl
Cl
Cl
O OHOO
OAu
Cl
Cl
Cl
Fast
OH
OH1. - H2O
2. - Cl
O OO
O O
O O
OOO
O O Au
Cl
Cl
Cl
O O
OO
OAu
Cl
Cl
Cl
[AuCl2] +- Cl
OO
OO
OO
OO
OO
- CO2
O OO
O O
O O
O
OO
O OO
OO
OO
O OO
O O
O O
O
OO
O OO
OO
OO
+ 3 [AuCl2]- [AuCl4]
- 2 Cl
O OO
O O
O O
O
OO
O OO
OO
OO
CPEG
CPEG - AuNPs
OO
AuNP
Auric chloride
PEG
Scheme S1. Scheme of synthesis of AuNPs using CPEG.
Electronic Supplementary Material (ESI) for Journal of Materials Chemistry BThis journal is © The Royal Society of Chemistry 2013
2. Scheme of RIF loaded AuNPs conjugated multiblock copolymer nanoparticles by W/O/W double emulsion technique
Step-1
Formation of W/O single emulsion
multi-blockcopolymer + RIF
CPEG-Au
+
Probe sonication
Electronic Supplementary Material (ESI) for Journal of Materials Chemistry BThis journal is © The Royal Society of Chemistry 2013
Step – 2
S
2: Formatio
(RIF
Scheme S2.
Ds
on of W/O/
F loaded Au
. Mechannanopar
Drug boundspace of Au
1. Aq2. Pro
/W double e
u-polymer n
nism of preprticles by W
d in the inteuNPs and po
q. PVA obe sonicati
emulsion
nanoparticl
aration of RW/O/W doubl
Don
erstitial olymer mat
ion
1. M2. R3. W4. V
le)
RIF and AuNle emulsion
Drug looselyn surface oDrug boun the polym
trix
Magnetic stiRemoval of Washing Vacuum dry
NPs loaded n technique.
y bound of polymer Nnd inside
mer matrix
irring organic solv
y
polymer
NPs
vent
Electronic Supplementary Material (ESI) for Journal of Materials Chemistry BThis journal is © The Royal Society of Chemistry 2013
During the W/O single emulsion,
The polymer-drug-AuNPs nanoconjugates and polymer-drug conjugates are formed on the small W/O emulsion droplets.
In this step,
During the probe sonication, the PEG surrounded AuNPs are detached from the CPEG-Au dendron and capped by the polymer matrix. The capping of AuNPs is favored due to the presence of PEG on AuNPs and the PEG directs the AuNPs to be capped by the multiblock copolymer.
When the multiblock copolymer is used, the capping ability of RIF and AuNPs is favored. When the pure PLGA is used, The PLGA precipitates in faster rate due to its hydrophobic nature and hence, the probability of capping the RIF and AuNPs is minimum resulting in lower drug loading efficiency.
During the W/O/W double emulsification, the small W/O single emulsion droplets form the secondary emulsion with PVA aqueous solution. In this stage, the PVA stabilizes the polymer-drug-Au nanoconjugates and polymer-drug nanoconjugates within a sphere. Hence, after the washing and vacuum dry, a spherical shape polymer NPs are obtained. The drug is present in three different environments in the Au conjugated polymer nanoparticle. In the structure of drug loaded Au-polymer NPs, three different colors have been used to indicate that the drug is present in three different environments.
Where,
Green particles denotes the drug on the surface of polymer NPs, blue particles denotes the drug inside the polymer matrix and red particles denotes the drug in the interstitial space of AuNPs and polymer matrix.
Electronic Supplementary Material (ESI) for Journal of Materials Chemistry BThis journal is © The Royal Society of Chemistry 2013
3. X
XPS traces
Fi
s of RIF loa
ig. S2. XPS
aded PLGA
traces of R
A-AuNPs na
RIF loaded P
anoconjuga
PLGA-Au N
ates
NPs (PSP0AuuR).
Electronic Supplementary Material (ESI) for Journal of Materials Chemistry BThis journal is © The Royal Society of Chemistry 2013
4. P
The pha
obtained
the curv
ng.h/mL
respecti
quantifi
bioavail
Pharmacok
armacokinet
d for PSPAu
ve (AUC0–∞
L and ng/m
vely. Since,
cation of t
lability of R
Fig.
kinetics res
tics values o
uR series N
∞) and maxi
mL respecti
, the Cmax v
the metabol
RIF is increa
S3. Histogr
ults of RIF
of DRIF, rif
NPs are given
imum conc
vely while
values obtain
lites may n
ased with low
ram of DRI
F metabolite
fampicin qu
n in the Tab
centration (C
those of R
ned for the m
not be accu
wer concent
F plasma co
es
uinone (RQ)
bles S1–S3
Cmax) values
RIF are ob
metabolites
urate. Howe
tration of th
oncentration
) and rifamp
and Figs. S
s of metabo
btained in µ
of RIF are
ever, it is t
he metabolit
n Vs Time p
picin N-oxi
3–S5. The a
olites are ob
µg.h/mL an
below 25 n
to be noted
tes.
profile.
ide (RNO)
area under
btained in
nd µg/mL
ng/mL, the
d that the
Electronic Supplementary Material (ESI) for Journal of Materials Chemistry BThis journal is © The Royal Society of Chemistry 2013
Figg. S4. Histoggram of RQ
Q plasma con
ncentration Vs Time pr
rofile.
Electronic Supplementary Material (ESI) for Journal of Materials Chemistry BThis journal is © The Royal Society of Chemistry 2013
Fig.. S5. Histoggram of RNO
O plasma co
oncentrationn Vs Time p
profile.
Electronic Supplementary Material (ESI) for Journal of Materials Chemistry BThis journal is © The Royal Society of Chemistry 2013
Table S1. Pharmacokinetics results of DRIF
samples AUC0-∞
(ng.h/mL) Cmax(ng/mL) Tmax(h) Relative bio
availability AUC0-∞DRIF/
AUC0-∞RIF Free RIF 342 11.5 10 1 0.0182 PSPAu0 2122 10.6 120 6.2 0.0038
PSPAu1 2113 8.6 120 6.1 0.0008
PSPAu2 518.1 8.7 48 1.51 0.0001
PSPAu3 525 9.1 48 1.53 0.0002
PSPAu4 1528 8.8 48 4.4 0.0007
AUC0–∞ - Area under the curve
Cmax - maximum concentration
Tmax - Time of maximum concentration
Table S2. Pharmacokinetics results of RQ
samples AUC0-∞
(ng.h/mL) Cmax
(ng/mL) Tmax(h) Relative bio
availability AUC0-∞RQ/
AUC0-∞RIF Free RIF 2774 19.45 48 1.0 0.148 PSPAu0 2895 19.72 48 1.04 0.0052
PSPAu1 3921 17.43 24 1.41 0.0015
PSPAu2 5210 23.57 5 1.87 0.0014
PSPAu3 4092 19.00 72 1.47 0.0015
PSPAu4 3991 17.9 10 1.43 0.0019
Table S3. Pharmacokinetics results of RNO
samples AUC0-∞
(ng.h/mL) Cmax(ng/mL) Tmax(h) Relative
bio availability
AUC0-∞RNO/
AUC0-∞RIF
Free RIF 0 - - - - PSPAu0 0 - - - -
PSPAu1 399 8.9 5 - 0.0001
PSPAu2 396 5.3 10 - 0.0001
PSPAu3 481 9.1 10 - 0.0001
PSPAu4 392 2.7 10 - 0.0001
Electronic Supplementary Material (ESI) for Journal of Materials Chemistry BThis journal is © The Royal Society of Chemistry 2013