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DOI: 10.1002/adma.200602794

Thermoresponsive “Particle Pumps”: Activated Release of

Organic Nanoparticles from Open-Cell Macroporous Polymers**
By Haifei Zhang* and Andrew I. Cooper*

A very wide range of useful organic molecules such as drugs
are poorly soluble in water and water-miscible organic sol-
vents.[1] As such, the utilization of water-insoluble active spe-
cies in aqueous systems is of broad relevance in areas such as
pharmaceuticals, nutraceuticals, and consumer products. The
preparation of organic nanoparticles from such actives pro-
vides a potential strategy for their deployment in water-based
formulations. Organic nanoparticles can be produced in the
form of solid powders (e.g., by wet milling, solvent precipita-
tion, spray freezing) or as aqueous dispersions (e.g., by emul-
sion evaporation, emulsification diffusion, or solvent displace-
ment methods).[1–3] In many applications it may be useful to
release the nanoparticles into an aqueous medium by using a
trigger. In this study, we describe a new and potentially gener-
ic route for the controlled release of organic nanoparticles
into aqueous solutions. This route combines successive poly-
merization and freezing steps for the “one pot” production of
thermoresponsive emulsion-templated poly(N-isopropyl acry-
lamide) (PNIPAM) materials which are loaded with organic
nanoparticles. The nanoparticles may then be released into
water on demand by raising the temperature above the lower
critical solution temperature (LCST) for PNIPAM, thus caus-
ing the material to contract and to “pump” the organic nano-
particles into the surrounding aqueous medium. LCST transi-
tions have been widely investigated in drug delivery;[4–6] for
example, to release indomethacin molecules from PNIPAM/
hydroxyapatite[7] and PNIPAM/silica composite matrices[8]
However, in those studies the organic active molecule (indo-
methacin) was molecularly entrapped in the swollen polymer
at low temperature. When the solution was heated above
LCST, the polymer matrix shrank and “squeezed” the indo-
methacin molecules into the larger pore channels in the inor-
ganic composite. The indomethacin molecules then diffused
slowly out into the surrounding phosphate buffer at pH 7.4.
By contrast, in our study the organic active exists as pre-
formed nanoparticles rather than individual molecules, which
– and expelled from pH-sensitive hydrogel microspheres by
[*] Dr. H. Zhang, Prof. A. I. Cooper
Department of Chemistry, University of Liverpool
Oxford Street, Liverpool, L69 7ZD (UK)
E-mail: zhanghf@liv.ac.uk; aicooper@liv.ac.uk
[**] This work was supported by the EPSRC (EP/C511794/1) and Univer-
sity of Liverpool (RDF 6014). HZ is a RCUK Academic Fellow. AIC is
a Royal Society University Research Fellow. We acknowledge Dr. Jim
Long and Dr. Dong Wang (IOTA NanoSolutions) for assistance with
DLS measurement and AFM imaging, respectively. Supporting In-
formation is available online from Wiley InterScience or from the
author.
is a significant advance in terms of processing poorly water-
soluble organic molecules. These organic nanoparticles are
then physically “pumped” from the pore structure to form a
stable aqueous nanodispersion upon contraction of the poly-
mer matrix. The utilization of two-phase emulsions during the
preparation (Fig. 1) makes it easier to choose a suitable sol-
vent for water-insoluble organic molecules. As such, our
method may be a very useful generic route for obtaining ma-
terials which can release organic substances. It was reported
(i) Polymerize
aqueous phase
(ii) Freeze
(iii) Freeze dry
(a) Concentrated O/W emulsion (b) Porous particle-loaded material
(c) Add water, T < LCST (d) Heat, T > LCST
Figure 1. Schematic showing preparation and release of organic nanopar-
ticles from a thermoresponsive emulsion-templated matrix. a) Formation
of concentrated O/W emulsion with organic material dissolved in oil
phase. b) (i) Aqueous phase is gelled by polymerization. (ii) Oil and water
are frozen and then removed by freeze-drying to produce organic nano-
composites (nanoparticles supported in macroporous structures).
c) Composite is swollen in water below LCST: Organic particles remain en-
trapped. d) Heating above LCST causes rapid contraction of polymer, and
“pumping” of organic nanoparticles into surrounding aqueous solution.
previously that inorganic nanocrystals (CdTe) were trapped
varying the surrounding pH.[9] In that study, the CdTe nano-
crystals were synthesized, loaded, and entrapped in the pre-
formed microspheres due to the physical entanglement of the
collapsed gel network. Our study represents the first example
of the triggered physical release of organic nanoparticles by
such a mechanism, and is broadly analogous to biological
mechanisms in which organisms such as sponges (Poriferans)
regulate the flow of particulate matter through their highly
porous feeding structures.[10]

Adv. Mater. 2007, 19, 2439–2444 © 2007 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim 2439
COMMUNICATION

A schematic of the materials preparation and activated par-

ticle release is shown in Figure 1. First, an oil-in-water (O/W)
emulsion was prepared following a similar procedure to that
which we reported before.[11] Oil Red (OR) was used as an
organic model material and cyclohexane (CH) was chosen as
the internal organic phase. The OR-CH solution was emulsi-
fied into an aqueous phase containing a monomer N-isopro-
pylacrylamide (NIPAM), a crosslinker N,N′-methylenebisac-
rylamide (MBAM), and a surfactant Triton X-405 firstly by
stirring and then by homogenizing. The emulsions were poly-
merized in an oven at 60 °C overnight. The sample was then
frozen in liquid nitrogen and transferred into a freeze dryer
for drying. Both CH and water were removed concurrently by
the process of freeze drying.[12,13] As a result of freeze drying,
OR nanoparticles were formed in the pore structure in a man-
ner which is broadly analogous to the preparation of organic
nanoparticles by emulsification-evaporation techniques.[3] It is
probable that the OR nanoparticles form a uniform coating
on the PNIPAM surface, as supported by FE-SEM imaging
(Fig. S1). Due to the low contrast between OR nanoparticles
and polymer support and the presence of the polymer surfac-
tant, it was difficult to identify unambiguously any given indi-
vidual particle as OR, although the marked difference in mor-
phology between the unloaded and loaded samples was clear
(Fig. S1).
A high internal phase emulsion (HIPE) was used to prepare
the emulsion-templated porous materials. The pore volumes
and pore size distributions were obtained using mercury intru-
sion porosimetry. The as-prepared material showed a high
pore volume (7.37 cm3 g–1) and bimodal pore sizes around
15 lm and 5 lm (Fig. 2a). It should be noted that the pore
sizes by mercury intrusion porosimetry indicate the window Figure 2. PNIPAM samples were soaked in water at 18 °C or heated
connecting the cells, not the diameter of the cells. In order to above the LCST. These samples were then frozen rapidly and freeze dried
investigate the thermoresponsive properties of the material for characterization. a) Pore volumes and pore size distributions as re-
corded by mercury intrusion porosimetry. b) SEM image for the sample
swollen in water, the polymer with a small amount of free
as prepared. c) SEM image for the sample treated by soaking in water at
water at 18 °C was frozen in liquid nitrogen rapidly before 18 °C. d) SEM image for the sample treated by soaking in water at 18 °C
freeze drying in order to “lock in” the swollen morphology. In for 2 h and then placed in water bath at 45 °C for 3 min.
a comparable experiment, a piece of swollen PNIPAM/OR
material contained in a glass tube was placed in a water bath
at 45 °C for 3 minutes and then placed into liquid nitrogen for of the prepared PNIPAM-OR composite with an average
a rapid freezing in order to lock in the collapsed morphology emulsion-templated “cell size” of around 15 lm. The image
above the LCST. The morphology of both materials was in- shown in Figure 2b represents the material in the dry, col-
vestigated after freeze drying. It can be seen from Figure 2a lapsed state. It can be seen that the pore sizes of the swollen
that the pore volume was increased a little when the material material were increased substantially to around 26 lm when
was soaked in water at 18 °C) and then frozen and freeze the as-prepared PNIPAM-OR was soaked and swollen at
dried. The pore size distribution was also changed and the 18 °C (cf., Fig. 2b and c). By contrast, when the swollen poly-
average size of macropores was increased to around 50 lm. mer was heated in water bath, the material shrank noticeably
When the material was soaked in water and then heated and the average pore size in the resulting freeze-dried materi-
above the LCST, the pore volume was dramatically decreased al was decreased to about 8 lm (Fig. 2d).
to around one fourth of the original water-swollen volume PNIPAM is a thermoresponsive polymer because of its hy-
(1.90 versus 7.80 cm3 g–1). This is consistent with the observa- drophobic isopropyl functionality.[14,15] Linear PNIPAM dis-
tion of the contraction of the polymer sample. The average solves in water at room temperature and can be precipitated
pore size was also decreased dramatically to around 1 lm. from solution by heating above the LCST (31 °C). For these
These samples were also characterized using scanning elec- crosslinked PNIPAM hydrogels, the materials are fully swol-
tron microscope (SEM). Figure 2b shows the porous structure len in water at room temperature and but contract to certain

2440 www.advmat.de © 2007 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim Adv. Mater. 2007, 19, 2439–2444
 COMMUNICATION
degree, depending on the macropore structure and crosslink-
ing levels, at elevated temperatures. Figure 2a and b and a
comparison of Figure 2c and d suggest that the emulsion-tem-
plated macropore size was indeed decreased dramatically by
heating above the LCST which is consistent with the sample
shrinkage observed. It should be noted, however, that rapid
freezing was adopted before freeze drying these materials:
this may also affect the precise nature of the pore structure.
As such, the structures shown in Figure 2 are indicative of the
substantial changes that occur during swelling and deswelling
but may differ somewhat from the actual structures in the wet
state.
Our aim in this study was to demonstrate that thermore-
sponsive polymer contraction can be used to expel nanoparti-
cles from a porous host. In principle, therefore, the more the
material can contract, the more effective the activated release
should be. We therefore targeted porous PNIPAM hydrogels
with a large pore volume by using a high internal phase O/W
emulsion (75 v/v % internal phase) as the template.[11] In or-
der to better understand the PNIPAM sample, a similar emul-
sion-templated crosslinked polyacrylamide (PAM) material 0.8

was tested in parallel as a non-thermoresponsive “control”

0.7 (g) Porous PAM-OR
12 m In at RT
(Fig. 3). PAM hydrogels are hydrophilic and expand strongly
50 m In at RT
in water but PAM does not exhibit an LCST phase transition 0.6 90 m In at RT
under the conditions studied here. In a preliminary test to 3 m In 45 ºC
UV Adsorption

demonstrate this concept, a sample of the PNIPAM material 0.5 Porous PNIPAM-OR
12 m In at RT
was soaked in water at room temperature overnight. There
0.4 50 m In at RT
was only very slight release of the OR nanoparticles from the 90 m In at RT
polymer matrix over a period of around 20 h. To demonstrate 0.3 3 m In 45 ºC
this concept more quantitatively, the release of the OR nano-
particles was analyzed using UV spectroscopy by comparing 0.2

PNIPAM and PAM samples over the same time scale. Fig-
0.1
ure 3a shows both polymers a few minutes after addition to
water at 18 °C (PAM sample on left; PNIPAM sample on 0.0
right). Figure 3b illustrates the effect of soaking both of these 300 400 500 600 700 800
1.2
Wavelength (nm)
(h)
1.0
OR released (normalized)

Figure 3. Comparsion of OR nanoparticles released from PAM-OR (left)

0.8 PNIPAM-OR
and PNIPAM-OR (right), respectively. Both samples were soaked in water PAM-OR
at 18 °C and then heated in a water bath at 45 °C. a) Immediately after
adding water at 18 °C. b) 50 min at 18 °C. c) 90 min at 18 °C. d) After 0.6
1 min in water bath at 45 °C. e) After 3 min in water bath at 45 °C.
f) Original dry state of both samples. g) Plot comparing the release of
OR from PAM-OR and PNIPAM-OR as measured using a UV plate read- 0.4
er. It should be noted that the last two traces of (“90 min at RT” and
“3 min in 45 °C”) for the PAM sample coincide because there was no
further change in the OR nanoparticle concentration after heating the 0.2 18 ºC
PAM sample for 3 min at 45 °C. (h) Release of OR nanoparticles from the
polymer matrix for 3 heating cycles normalized to the maximum UV ad-
sorption of OR from PNIPAM-OR and PAM-OR, respectively. The pat- 0.0
0 30 60 90 120 150 180 210 240
terned orange rectangle areas represent the heating periods at 45 °C after
which the samples were allowed to cool back to ambient temperature. Time (min)

Adv. Mater. 2007, 19, 2439–2444 © 2007 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.advmat.de 2441
COMMUNICATION
OR-loaded polymers in water for 50 minutes at 18 °C in the
absence of any agitation. It can be observed that the water
phase was essentially colorless for the PNIPAM-OR system
while the PAM-OR released a sufficient quantity of OR nano-
particles causing the solution to become strongly colored
(Fig. 3b). In fact, UV analysis showed that a very small quan-
tity of OR was dispersed into the water for the PNIPAM sys-
tem, but clearly very much less than in the case of the PAM
sample. We ascribe this to weakly physisorbed OR nanoparti-
cles on the external surface of the PNIPAM composite being
washed into the aqueous phase to form a very dilute disper-
sion. Clearly, the PAM sample released far more OR than the
PNIPAM sample under these conditions—even though both
polymers are water-swollen at this temperature—we believe
that this may be a result of the affinity for the hydrophobic
OR particles being much higher for the more hydrophobic
PNIPAM pore structure. After 90 minute at 18 °C, the red col-
or was still barely visible for the PNIPAM system while the
color was intense for the PAM sample (Fig. 3c). At this point,
both the samples were placed simultaneously into a 45 °C
water bath—that is, above the LCST for PNIPAM. After 1
minute the PAM system appeared to be unchanged. By con-
trast, the PNIPAM sample began to shrink dramatically in
size and red “clouds” of OR particles were observed to be re-
leased from the sample upon contraction (Fig. 3d). A video in
the Supporting Information for this paper (Movie_S1) shows
clearly this dramatic contraction/expulsion process for PNI-
PAM-OR sample of this type. After 3 minutes in water bath
at 45 °C (Fig. 3e), the PNIPAM-OR composite had contracted
to approximately 25 % of its water-expanded dimensions and
a more intense red aqueous nanodispersion was formed. A
stable aqueous nanodispersion was formed by the release of
OR nanoparticles into water. These nanoparticles were stabi-
lized in water by the polymer surfactant, Triton-X405, which
also diffused out of the polymer matrix into the surrounding
aqueous phase. Figure 3f shows both the dry samples before
soaking in water, as a reference. The release of the OR nano-
particles was also monitored qualitatively using a UV-visible
spectrometer. The adsorption peak at 514 nm should be used
only semi-quantitatively since the extinction coefficient for
nanodispersed OR was not known, although a quantitative
determination was made for subsequent systems (see below).
Figure 3g confirms that, at 18 °C, OR was released steadily
from the PAM sample over 90 minutes whereas very little re-
lease occurred from the PNIPAM sample. Upon heating in
45 °C water bath the adsorption band for OR grows dramati-
cally for the PNIPAM system, thus confirming the activated
“pumping” release mechanism to be specific to the thermore-
sponsive polymer. It should be noted that the pore geometry
(and hence surface area) for the PAM and PNIPAM samples
were not identical. That said, we believe that the very slow re-
lease of OR nanoparticles from PNIPAM at 18 °C cannot sim-
ply be explained by such differences and that the “pumping”
effect caused by thermoresponsive shrinkage of PNIPAM is
much more dominant than effects relating to differences in
pore structure or surface area.
2442 www.advmat.de © 2007 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
We also attempted to carry out “multicycle” release of OR
nanoparticles from these materials. Figure 3h shows the nor-
malized profile of OR nanoparticles released from both PNI-
PAM-OR and PAM-OR materials over three heating cycles.
It can be seen that the rate of release of OR nanoparticles
from the PAM materials was approximately linear with time
and showed very little dependency on the heating cycle. By
contrast, the PNIPAM-OR system exhibits a burst release of
OR nanoparticles each time that the sample is heated, at least
for three such cycles. It was observed that fewer OR nanopar-
ticles were released from the second and, particularly, the
third heating step in comparison with the first, suggesting that
most of the “releasable” OR in these particular samples was
expelled after three “pumping” cycles.
The two samples illustrated in Figure 3 were prepared at
different crosslinking densities. This was because porous PAM
samples prepared at a crosslinking density of 1 % were so
swellable and lacking in mechanical strength that it was not
practical to investigate the release of the OR nanoparticles.
Thus, in order to make a direct, like-by-like comparison, 2 %
crosslinked PNIPAM-OR and PAM-OR were prepared under
similar conditions. UV-visible measurements (Fig. S2) showed
similar trend to those illustrated in Figure 3g although the
contracting and therefore pumping capacity of the PNIPAM
sample was decreased at this higher crosslinking density.
The OR nanoparticles released from the samples were char-
acterized by FE-SEM using a scanning transition electron mi-
croscope detector (STEM) in the dry state and also in situ in
the aqueous phase by dynamic light scattering (DLS). A solu-
tion of OR in cyclohexane with a concentration of 0.02 wt %
was used to form the nanoparticles to give a nominal loading
of 2.09 mg g–1 OR in the polymer material. Figure 4a shows
the OR nanoparticles released from a 1 % crosslinked PNI-
PAM-OR system. The diameters of the nanoparticles were es-
timated by STEM imaging to be in the range of 50–150 nm.
DLS measurements (Fig. 4c) showed a bimodal distribution
with an intense peak centered at around 300 nm and a weak
peak at 50 nm. We assign the DLS peak at 300 nm to the or-
ganic nanoparticles by comparison with the DLS plot for a
“blank” sample (Fig. S3) in which the weaker peak at 50 nm
could also be observed, presumably arising from aggregates of
the surfactant or from a small fraction of soluble PNIPAM
which also diffused into the water during soaking.
The low loading of OR in these composites was a result of
the low solubility of OR in cyclohexane (< 0.35 wt %). The
OR loading could be increased substantially by adding a small
amount of acetone as a cosolvent. In this case, OR concentra-
tions of up to 0.48 wt % in cyclohexane-acetone solutions
could be used to generate the O/W emulsions. Thus the total
loading of OR in the dry PNIPAM composite could reach
50 mg g–1 (5 wt %). As before, the OR nanoparticles in these
more highly loaded composites could be released into water
by thermoresponsive pumping. In this case, the resulting or-
ganic nanodispersions that were formed were much more con-
centrated (Fig. S4). The STEM image in Figure 4b shows the
nanoparticles released from a PNIPAM-OR composite pre-
Adv. Mater. 2007, 19, 2439–2444

18
16 (c) (d)
80
14
Intensity (%)
Intensity (%)
12 60
10
8 40
6
4 20
2 throughout. It was, however, possible to release ad-
0 0
10 100 1000 100
Particle size (nm) Particle size (nm)
Figure 4. Characterization of OR nanoparticles by STEM (a,b) and DLS (c,d). a) STEM
image of OR nanoparticles from 1 % crosslinked PNIPAM-OR (OR loading
2.09 mg g–1). b) STEM image of OR nanoparticles from 1 % crosslinked PNIPAM-OR
(OR loading 15.73 mg g–1). c) DLS plot of OR nanoparticles for the sample shown in
(a). d) DLS plot of OR nanoparticles for the sample shown in (b).
pared using a 0.15 wt % OR solution to give an OR nanopar-
ticle loading of 15.7 mg g–1 in the polymer material. These par-
ticles have diameters in the range of 50–150 nm—that is, very
similar to the particles formed in the composites at lower OR
loadings. DLS measurements were also carried out in situ to
monitor the release of the OR nanoparticles from these more
concentrated PNIPAM-OR composites. The temperature was
raised slowly from 18 °C to 36 °C in 2 °C steps and a DLS mea-
surement performed in each case 10 min after reaching ther-
mal equilibration. The sample was kept at 18 °C for 15 min-
utes before taking the first measurement. Figure 4d illustrates
the change in the apparent average OR nanoparticle size in
the nanodispersion as the temperature was raised and more
particles were expelled. (A plot for the whole temperature
range is shown in Fig. S5.) It was apparent that there was no
measurable scattering intensity at 18 °C—that is, very few par-
ticles were released. When the temperature was increased to
20 °C, a small peak was observed at around 160 nm which
may correspond to smaller, weakly physisorbed particles
being released from the surface of the material. In the temper-
ature range 22–26 °C, further particles were released as the
polymer contracted and the LCST was approached (Fig. 4d).
The LCST for linear PNIPAM is around 31 °C but can be sen-
sitive to a number of factors such as crosslinking density and
[14,16–18]
the presence of surfactants.
We observed that very few additional OR nanoparticles
were released after the third heating cycle (Fig. 3h), despite
the fact that OR clearly remained in the polymer (as evi-
denced by its residual red coloration). The percentage of the
total available OR nanoparticles released from PNIPAM ma-
Adv. Mater. 2007, 19, 2439–2444 © 2007 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
COMMUNICATION
trix in the first heating cycle was calculated to be
28 % for a material loaded with 2.09 mg g–1 OR
and 13 % for a similar material loaded at
15.73 mg g–1.[19] The failure to release all of the OR
nanoparticles from the sample might be due to the
fact that the polymer surface is energetically het-
erogeneous and that the hydrophobic OR nanopar-
ticles have stronger interaction with some parts of
the surface than others. Alternatively, the contrac-
tion observed above the LCST may simply not be
26 ºC effective enough to squeeze out all of the OR
24 ºC
22 ºC nanoparticles from the bulk of the material, al-
20 ºC
18 ºC though there was no evidence in general of a resid-
ual “core” of particles in the centre of the compos-
ite but rather a more uniform distribution
ditional OR nanoparticles simply by soaking the
1000 10000 PNIPAM-OR composite in cyclohexane and freeze
drying again. This may suggest that there is a distri-
bution of particle sizes formed after freeze-drying
and that the larger (or indeed smaller) species are
physisorbed more strongly and thus harder to re-
lease from the composite.
In summary, we have demonstrated a new meth-
od for the triggered release of water-insoluble
organic species in the form of nanoparticles. Pre-
liminary experiments with water-insoluble drugs (e.g., indo-
methacin, Fig. S6) suggest that the method is quite general
and could be developed further for a variety of applications.
Experimental
Chemicals: Oil Red O (OR), ammonium persulfate (APS, 98+ %),
N-isopropyacrylamide (NIPAM, 97 %), N,N′-methylenebisacrylamide
(MBAM, 99 %), Triton X-405, acrylamide (AM, 99+ %), and
N,N,N′,N′-tetramethylethylenediamine (TMEDA, 99 %) were pur-
chased from Sigma-Aldrich and used as received. Indomethacin
(IMC, ≥ 99.0 % TLC) was purchased from Fluka and use as received.
Preparation of the Materials: An aqueous solution of NIPAM and
MBAM (1.0 M and 0.01 M) was prepared. The typical procedure for mak-
ing 1 % crosslinked PNIPAM-OR was: to add 2.0 mL NIPAM/MBAM
solution, 0.3 mL Triton X-405 and 0.1 mL 10 wt % APS aqueous solu-
tion in turn while stirring, after which 6.0 mL 0.02 wt % OR-CH solu-
tion (or 0.48 wt % OR-CH-acetone with acetone:CH = 9:1 w/w) with
30 ll TMEDA was slowly dropped into the aqueous phase while stirring
vigorously. After stirring for 5 min, the emulsion was homogenzied for
1.5 min at scale 3 using a Fisher Brand homogenizer. The emulsion was
then placed in an oven at 60 °C for at least 12 h. The polymerized sam-
ple was allowed cool down at room temperature, frozen rapidly in liquid
nitrogen, and then freeze dried in a freeze dryer (LyoLab 3000, Heto).
This procedure was followed to make other samples but different mono-
mer solutions were used. For example, 2 % crosslinked PAM–OR was
prepared using 4 M AM/0.08 M MBAM solution. The more highly cross-
linked PAM-OR shown in Figure 3 was prepared using 4 M AM/MBAM
0.5 M solution.
Characterization: Pore volume and pore size distributions were re-
corded by mercury intrusion porosimetry using a Micromeritics Au-
topore IV 9500 porosimeter over a pressure range of 0.10 psia to
60 000 psia. Intrusion volumes were calculated by subtracting the in-
trusion arising from mercury interpenetration in large spaces (pore
www.advmat.de 2443
COMMUNICATION
size > 150 lm) from the total intrusion. A Hitachi S-4800 SEM with a
STEM detector was used to investigate the macropore structure and
the dried OR nanoparticles, respectively. The polymer monolith was
sectioned and adhered to a SEM stud using double-sided carbon tape.
The polymer sample was then coated with gold using a sputter-coater
(EMITECH K550X) for 3 min at 40 mA. For imaging using a STEM
detection, 5 ll of aqueous OR nanodispersion was dropped onto a
TEM grid which allowed to dry overnight. The hydrated diameter of
the OR nanoparticles in water was measured by dynamic light scatter-
ing (DLS) using Malvern Zetasizer Nano S at 25 °C. At least 3 mea-
surements were taken and the average data were obtained. The UV
tests were performed using a UV plate reader (lQuant, Bio-Tek In-
strument Inc.). Photographs and videos were recorded using an Olym-
pus C-5060 wide zoom digital camera.
Received: December 6, 2006
Revised: February 9, 2007
Published online: August 14, 2007
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[18] Y. H. Bae, T. Okano, S. W. Kim, Pharm. Res. 1991, 8, 531.
[19] The OR UV calibration data were obtained by fully dissolving OR
in a mixture of 1-methoxy-2-propanol and water (80:20 w/w). For
UV measurements on the OR release profile, 0.1 mL of the OR
nanodispersion was sampled and mixed with 0.435 mL 1-methoxy-2-
propanol to give the solvent mixture in the right ratio. The percent-
age of release was obtained by calculating the OR in water and the
OR in the original PNIPAM matrix.
Adv. Mater. 2007, 19, 2439–2444