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Dye Loading of Amphiphilic Poly(organosiloxane) Nanoparticles.

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Angewandte
Chemie
Communications
The loading of amphiphilic poly(organosiloxane) nanoparticles
with hydrophilic dyes in organic solvents depends inter alia on the
construction of the nanoparticles (core–shell, hollow spheres), on the
amphiphilicity, is adjustable by synthesis, and on the method of the
phase transfer. For more information see the Communication by M.
Maskos et al. on the following pages.
Angew. Chem. Int. Ed. 2003, 42, 1713
DOI: 10.1002/anie.200250288
2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1713
Communications
Dye Incorporation in Polymers
Dye Loading of Amphiphilic
Poly(organosiloxane) Nanoparticles**
Nadja Jungmann, Manfred Schmidt, Jochen Ebenhoch,
Johann Weis, and Michael Maskos*
Interest in amphiphilic core–shell nanoparticles is increasing
continually and their use for possible applications in which,
for example, they are loaded with small molecules or even
proteins is under discussion.[1–4] Typical examples are dendrimers,[5] cyclodextrins,[6] star-shaped block copolymers,[7]
and cross-linked block copolymer micelles.[8] The covalent
construction of these macromolecular-based systems inhibits
the structural self-disintegration of the nanoparticles. However, the synthesis of these structures is usually timeconsuming, and, in the case of dendrimers and cyclodextrins,
their size is limited to a few nanometers. Non-cross-linked
block copolymer micelles,[9] polyelectrolyte capsules,[10] and
liposomes[11] are potential and partially evaluated capsule
systems, which form from their constituent subunits as a result
of specific interactions. Unlike the covalent systems they have
the undesirable tendency to break down under certain
circumstances through changes in the external conditions.
These structures are usually of 50–100 nm up to micrometers
in size. In the case of liposomes, in particular, the amphiphilicity of the structures created is determined by the starting
components used and normally cannot be varied, or only to a
limited extent.
Unlike the described nanoparticles the novel amphiphilic
poly(organosiloxane) nanoparticles are very versatile with
respect to the variation of the many parameters that affect
loading, and thus allow systematic investigation. In particular,
it was possible to prepare different core–shell arrangements.
Figure 1 illustrates this schematically for the spherical nanoparticles we have investigated.
The nanoparticles were prepared by the hydrolysis and
condensation of dialkoxydialkyl- and trialkoxyalkylsilanes in
aqueous dispersion. After surface modification they may be
re-dispersed in organic solvents such as toluene.[12] Core–shell
arrangements are formed through sequential monomer
addition. Quaternary ammonium groups in the siloxane
network provide the hydrophilic character of the core
(QCx-S) or the inner shell (QC-Sx-S, QSx-S). In the sample
categorization, x correlates with the number of quaternary
[*] Dr. M. Maskos, Dipl.-Chem. N. Jungmann, Prof. Dr. M. Schmidt
Institut f(r Physikalische Chemie
Universit+t Mainz
Welder-Weg 11, 55099 Mainz (Germany)
Fax: (+ 49) 6131/392-2970
E-mail: maskos@mail.uni-mainz.de
Dr. J. Ebenhoch, Dr. J. Weis
Wacker-Chemie GmbH
84480 Burghausen (Germany)
[**] This work was supported by the BMBF (FKZ 03C0288A8), the Fonds
der Chemischen Industrie, and Wacker-Chemie GmbH (Germany).
1714
2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Figure 1. Schematic representation of the amphiphilic poly(organosiloxane) nanoparticles (see text for details). Also shown are the basic
building blocks of the core and the shells.
ammonium groups in the network. The outer hydrophobic
shell ensures the solubility in organic solvents. In addition to
the comparatively simply constructed core–shell nanoparticles more complex spherical arrangements can also be built
up by the synthesis used. On the one hand, it is possible in this
way to prepare a flexible core of siloxane chains (QC-Sx-S), in
which the chains are bonded chemically to the surrounding
shell. On the other hand, nonbonded chains can be removed
from the core, to leave hollow spheres (QSx-S). A prerequisite for this is an adequate pore size in the surrounding shell
network, which can also be adjusted during synthesis.[13] These
chemically similar but differently constructed amphiphilic
nanoparticles are used to investigate the loading with hydrophilic dyes as low-molecular-weight model compounds. The
difference in construction permits the investigation of the
dependency of dye uptake on the respective arrangement.
Furthermore, as previously described, the amphiphilicity of
the nanoparticles can also be adjusted during synthesis by
altering the number of quaternary ammonium groups, which
allows the investigation of the nature of the interaction
between substrate and nanoparticle.
Dye loading of the amphiphilic poly(organosiloxane)
nanoparticles is carried out by solid/liquid or liquid/liquid
DOI: 10.1002/anie.200250288
Angew. Chem. Int. Ed. 2003, 42, 1714 – 1717
Angewandte
Chemie
phase transfer. In the solid/liquid phase transfer the dye is
added as a solid to the dispersion of the nanoparticles in
toluene. In liquid/liquid phase transfer an aqueous solution of
the dye is covered with a layer of the nanoparticle dispersion.
Diffusion of the dye into the nanoparticle then takes place.
The first visual indication of successful loading is the
coloration of the toluene phase. The schematic representations of the respective phase transfer and photographs of a
number of experiments are illustrated in Figure 2.
It can be readily seen with the naked eye that the loading
with both basic parafuchsin, a cationic dye, and thymol blue,
an anionic dye, is dependent on the number of quaternary
ammonium groups, and grows with increasing number. In
contrast, the control experiments with nanoparticles that
contain no quaternary ammonium groups and with pure
toluene show no coloration. Encapsulation occurs primarily
independently of the choice of phase transfer. In a comparable manner both the anionic dyes calmagite and brilliant
sulfaflavin as well as the anionically and cationically charged
dye sulforhodamine B and the pyrene dye pyrene-1-sulfonic
acid are also taken up into the nanoparticles successfully.
Dye uptake is also evident in the UV/Vis spectrum. A
number of representative spectra of the toluene phases after
loading with dye are illustrated in Figure 3. The spectra were
measured two weeks after dye addition since prolongation of
the experiments led to no change in dye uptake, regardless of
the method of phase transfer.
Figure 3. UV/Vis absorption spectra of the respective toluene phase
after loading with dye. c x = 12; a: x = 8; g: x = 4; d: C12S; e: toluene. s/l = solid/liquid phase transfer, l/l = liquid/liquid
phase transfer. dyes: BSF = brilliant sulfaflavin, FBH = basic parafuchsin, PY = pyrene-1-sulfonic acid, TB = thymol blue.
Figure 2. Solid/liquid (A) and liquid/liquid phase transfer (B) for loading the amphiphilic poly(organosiloxane) nanoparticles (Q spheres)
with the respective dye. The identical experiments carried out with
poly(organosiloxane) nanoparticles which contain no quaternary ammonium groups in the interior (C12-S) and with pure toluene are
shown in the photographs for comparison. Both show no coloration.
Angew. Chem. Int. Ed. 2003, 42, 1714 – 1717
For all the dyes and nanoparticles used loading of the
nanoparticles with the respective dye by both solid/liquid and
liquid/liquid phase transfer increases with the number of
quaternary ammonium groups in the nanoparticle. The
corresponding comparison of the two methods of phase
transfer shows, however, that lower intensities are observed
by UV/Vis spectroscopy for solid/liquid phase transfer. In
contrast, the control experiments show almost no absorption
in the range of the respective coloration in all cases.
It may be noted at this juncture that ionic interactions
between the positively charged ammonium groups in the
nanoparticles and the negatively charged groups of the dye
are not solely critical for the loading of nanoparticles since the
cationic, basic parafuchsin is taken up in addition to the
anionic dyes.
Quantitative analyses of the UV/Vis absorption spectra
were employed to draw more detailed conclusions. However,
because of the poor solubility of the dyes in toluene this is not
possible in the organic solvent since no calibration can be
carried out. Instead, the loading of the nanoparticles with the
respective dye was determined indirectly by the reduction in
the absorption of the aqueous phase after liquid/liquid phase
transfer. The results are collated in Table 1.
www.angewandte.org
2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1715
Communications
which contain the poly(dimethylsiloxane) chains in their core occupies
a middle position in all cases.
Sample
nN[b]
BSF
CM
FBH
SRB
TB
ndye[c] ndye/nN ndye
ndye/nN ndye ndye/nN ndye ndye/nN ndye ndye/nN
The size of the dye relative to the
mesh width of the siloxane network
QC4-S
0.7
1.4
2.0
6.4
9.1
0.8
1.1
0.3
0.4
6.3
9.0
of the nanoparticles is also of conQC8-S
1.1
2.9
2.6
7.3
6.6
1.1
1.0
0.3
0.3
8.8
8.0
siderable importance for loading
QC12-S
4.4
9.0
2.0
8.1
1.8
3.8
0.9
4.3
1.0
9.6
2.2
QC-S4-S
1.1
–
–
6.7
6.1
–
–
–
–
4.7
4.3
since the dye must diffuse through
QC-S8-S
1.9
1.4
0.7
8.4
4.4
–
–
–
–
6.3
3.3
the outer shell in every case.[13] The
QC-S12-S 5.9
6.4
1.1
10.9 1.8
2.5
0.4
4.3
0.7
9.4
1.6
dyes used do not differ significantly
QS4-S
2.2
2.2
1.0
5.9
2.7
0.5
0.2
4.9
2.2
from each other in respect of their
QS8-S
4.8
5.3
1.1
–
–
1.0
0.2
–
–
2.5
0.5
size. Only for sulforhodamine B, the
QS12-S
6.1
5.5
0.9
13.7 2.2
1.6
0.3
2.9
0.5
6.5
1.1
most sterically demanding of the
1
[a] Concentration of the nanoparticle in toluene (5 mL): c = 2.0 g L , concentration of the dye solutions
dyes investigated, is the mesh width
(in each case 5 mL): cBSF = 2.26 g L 1, cCM = 4.92 g L 1, cFBH = 1.30 g L 1, cSRB = 3.60 g L 1, cTB = 5.58 g L 1.
of the nanonetwork presumably not
BSF = brilliant sulfaflavin, CM = calmagite, FBH = basic parafuchsin, SRB = sulforhodamine B,
large enough to achieve a high
TB = thymol blue, sodium salt. [b] nN = amount of quaternary ammonium ions in mmol per 10 mg of
degree of loading. Control experinanoparticle.[12] [c] ndye = amount of dye in mmol per 10 mg of nanoparticle. No data: nanoparticles
partially precipitated at the interface.
ments with sterically demanding
dyes such as reactive red 120, with
which no coloration of the dispersed
nanoparticles in toluene occurs, confirm this observation.
To achieve a high as possible loading in these experiments
If the loading values at identical particle architecture are
the aqueous phase contained significantly more dye than
compared, an increase in the loading with increasing number
could be taken up into the nanoparticles in total. The loading
of quaternary ammonium groups is revealed for all dyes. At
of the amphiphilic nanoparticles with pyrene-1-sulfonic acid
the same time the quotient ndye/nN usually falls. The increase
could not be determined quantitatively by UV/Vis spectroscopy of the aqueous phase, however, since the reduction in
in the number of quaternary ammonium groups effects a
absorption compared with the starting concentration was too
suppression of the influence of the local network polarity in
small and consequently the changes lay within the range of
favor of the ionic interaction. Unfortunately, the expected
measurement error. The amount of the respective dye taken
loading saturation as a function of the number of quaternary
up was determined by prior calibration.
ammonium groups could not be achieved since the increase in
If the different dyes are compared it emerges that the two
the proportion of quaternary ammonium groups leads to
anionic dyes calgamite and thymol blue have the highest
irreversible aggregation of the growing nanoparticles during
uptake values, followed by brilliant sulfaflavin. In contrast,
synthesis.
much lower values are obtained for basic parafuchsin and
That specific interactions are vital for loading can be
sulforhodamine B. Especially remarkable is the loading of
inferred from two further observations. On the one hand,
QS12-S with calgamite. In this case it is possible to incorpoduring loading of the nanoparticles with brilliant sulfaflavin,
rate 50 % of the dye into the spheres relative to the weight of
calmagite, and thymol blue by liquid/liquid phase transfer a
nanoparticles used. If merely the aforementioned specific
deficiency of dye (relative to the maximum amount which can
ionic interactions were responsible for the loading this should
be incorporated) leads to complete decoloration of the
be directly reflected in the relationship between the number
aqueous phase. On the other hand, a comparison of the
of dyes incorporated (ndye) and the ammonium groups present
methods of phase transfer reveals that less dye is normally
taken up by solid/liquid phase transfer than by liquid/liquid
in the nanoparticles (nN). The respective quotient ndye/nN, for
phase transfer. This suggests an effect of the water present on
which a theoretical ratio of ndye/nN = 1 would be expected, is
the local polarity in the nanoparticles. The interactions of, for
also given for the corresponding experiments in Table 1. For
example, calmagite incorporated into QS12-S are so strong
calmagite and thymol blue the quotient lies significantly
that the dye could not be removed from the nanoparicle even
above the theoretical value. In contrast, the corresponding
by repeated ultrafiltration in THF, a good solvent for
quotients ndye/nN for the dye brilliant sulfaflavin lie close to
calmagite. This behavior and the pronounced solvatochromic
the expected theoretical value. For sulforhodamine B lower
shift in the absorption spectrum of a number of dyes after
values are obtained, and for basic parafuchsin unexpectedly
encapsulation are the subject matter of on-going research.
high values since it is a cationic dye which should actually
In summary, it can be demonstrated that it is possible to
exhibit no attractive ionic interactions. The loading of the
incorporate hydrophilic dyes in the interior of amphiphilic
nanoparticles with further cationic dyes is currently under
poly(organosiloxane) nanoparticles. In addition to ionic
investigation.
interactions the local polarity of the siloxane network, the
It may be concluded from these results that in addition to
size of the dye in relation to the mesh width of the network,
ionic interactions the local polarity within the nanoparticles is
and the method of phase transfer are critical for the extent of
of pivotal importance for loading. The hollow sphere systems
loading. By variation of these parameters up to 50 % dye
QSx-S are especially suitable for loading with calmagite,
relative to the dead weight of the nanoparticles can be
whereas the other dyes prefer QCx-S nanoparticles with their
encapsulated in the siloxane network.
more homogeneous construction. The loading into QC-Sx-S,
Table 1: Quantification of the dye uptake by liquid/liquid phase transfer into the amphiphilic
poly(organosiloxane) nanoparticles by UV/Vis spectroscopy of the aqueous phase.[a]
1716
2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
Angew. Chem. Int. Ed. 2003, 42, 1714 – 1717
Angewandte
Chemie
Experimental Section
The synthesis of amphiphilic nanoparticles is described in detail in
reference [12] . The preparation is based on the hydrolysis and
cocondensation of dialkoxydialkylsilane (D) and trialkoxyalkylsilane
(T) in aqueous dispersion by sequential addition of monomer
mixtures in the presence of a surfactant. Saturation of reactive silanol
or silanolate groups prevents the aggregation of the particles and
permits the transfer into toluene as re-dispersable nanoparticles. The
use of chloromethylphenyltrimethoxysilane (ClBz-T) in the core (C)
or in the inner shell (S) leads after polymer-analoguous quaternization (Q) with dimethylaminoethanol to the amphiphilic poly(organosiloxane) nanoparticles. The mass fraction of ClBz-T relative to the
total amount of monomer is designated by an x in the sample code.
Thus QC4-S, for example, is a nanoparticle with a fraction of 4 %
ClBz-T in the core, with QC-S8-S the nanoparticles have a fraction of
8 % ClBz-T in the inner shell. With QC-Sx-S and QSx-S the D units
are first condensed to chains, which in the case of QSx-S are
prevented from reacting with subsequently added monomer by the
addition of monoalkoxysilanes. By the use of mixtures of D and T in
the construction of the shells these chains can diffuse out of the
interior after transfer into toluene and are removed by ultrafiltration.
In QC-Sx-S the chains remain in the interior since they are bonded
covalently to the surrounding shell.
Solid/liquid phase transfer: The dye (10 mg) was added to a
dispersion of the amphiphilic poly(organosiloxane) nanoparticles
(10 mg) in toluene (5 mL). After two weeks the UV/Vis spectra were
recorded with a Lambda 17 spectrophotometer (Perkin Elmer).
Liquid/liquid phase transfer: The solution of the respective dye in
water (5 mL; concentration see Table 1) was carefully covered with a
dispersion of the amphiphilic nanoparticles (10 mg) in toluene
(5 mL). After two weeks the UV/Vis spectra of the toluene and
aqueous phases were recorded. The reduction in the absorption of the
aqueous phase was determined quantitatively by comparison with a
calibration curve of the dye in water.
[10] a) X. Y. Shi, F. Caruso, Langmuir 2001, 17, 2036; b) O. P.
Tiourina, A. A. Antipov, G. B. Sukhorukov, N. L. Larinova, H.
MLhwald, Macromol. Biosci. 2001, 1, 209.
[11] C. Leonetti, A. Biroccio, B. Benassi, A. Stringaro, A. Stoppacciaro, S. C. Semple, G. Zupi, Cancer Gene Ther. 2001, 8, 459.
[12] N. Jungmann, M. Schmidt, M. Maskos, J. Weis, J. Ebenhoch,
Macromolecules 2002, 35, 6851.
[13] a) C. Roos, M. Schmidt, J. Ebenhoch, F. Baumann, B. Deubzer, J.
Weis, Adv. Mater. 1999, 11, 761; b) O. Emmerich, N. Hugenberg,
M. Schmidt, S. Sheiko, F. Baumann, B. Deubzer, J. Weis, J.
Ebenhoch, Adv. Mater. 1999, 11, 1299.
Received: October 2, 2002 [Z50288]
.
Keywords: chromophores · colloids · materials science ·
nanostructures · polymers
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Angew. Chem. Int. Ed. 2003, 42, 1714 – 1717
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2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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