Note: Descriptions are shown in the official language in which they were submitted.
CA 02387476 2002-05-24
50057-3
Microencapsulation of Polar Liquids in Copolymer Shells
Field of the Invention
A technique for encapsulation of polar organic solvents
using Atom Transfer Radical Polymerization (ATRP) by
suspension polymerization was developed to encapsulate
diphenyl ether (solubility parameter, 8 = 20.9 MPal~2) for
the first time. To encapsulate polar core-oils an
amphiphilic polymer is required that has low interfacial
tensions with both the oil phase and the water phase.
Poly(methyl methacrylate-co-poly(ethylene glycol)
methacrylate) (PMMA-co-PegMA) was prepared in suspension
polymerization conditions. Use of ATRP ensures that the
water soluble comonomer, PegMA, is incorporated into every
polymer chain throughout the polymerization reaction so that
all chains possess the desired amphiphilic character.
Crosslinking of PMMA-co-PegMA with diethylene glycol
dimethacrylate (DegDMA) yielded hollow capsular particles at
31 mold PegMA in the terpolymer. Particles prepared with
similar monomer feed ratios by conventional free radical
polymerization did not exhibit a core shell structure
confirming the need for a living polymerization to ensure
the preparation of an amphiphilic copolymer in suspension
polymerization conditions.
Atom Transfer Radical Polymerization (ATRP)
Atom transfer radical polymerization is a
controlled/"living" polymerization based on the use of
radical polymerization to convert monomer to polymer.
Although many of the polymer types described have been
prepared using other living polymerizations, researchers
have been striving to develop a living radical
1
CA 02387476 2002-05-24
50057-3
polymerization for nearly 40 years. An alternative was
sought because other types of living polymerizations are
severely limited by many factors: only a small number of
monomers can be used, the reactions are sensitive to
moisture, and two or more monomers cannot be randomly
copolymerized. Radical polymerization, in contrast, can
polymerize hundreds of monomers, can copolymerize two or
more monomers, and can be performed in water as emulsions or
suspensions. Controlled/"living" radical polymerization
promised to overcome these limitations and provide a method
to maximize the potential of living polymerizations.
The Matyjaszewski research group was the first to develop a
controlled/"living" polymerization that used a simple,
inexpensive polymerization system. It is capable of
polymerizing a wide variety of monomers, is tolerant of
trace impurities (water, oxygen, inhibitor), and is readily
applicable to industrial processes. The system that was
developed was termed Atom Transfer Radical Polymerization
(ATRP). ATRP is a robust system that has generated much
interest among polymer chemists in both industry and
academia. Science Watch, a trade journal, has recently
listed three ATRP papers among the top ten cited papers in
chemistry today.
The control of the polymerization afforded by ATRP is a
result of the formation of radicals that can grow, but are
reversibly deactivated to form dormant species. Reactivation
of the dormant species allows for the polymer chains to grow
again, only to be deactivated later. Such a process results
in a polymer chain that slowly, but steadily, grows and has
a well-defined end group (for ATRP that end group is usually
an alkyl halide).
2
CA 02387476 2002-05-24
50057-3
The initiator is generally a simple, commercially available,
alkyl halide. The catalyst is a transition metal that is
complexed by one or more ligands; the catalyst does not :need
to be used in a one-to-one ratio with the initiator but can
be used in much smaller amounts. The deactivator can be
formed in situ, or for better control, a small amount
(relative to the catalyst) can be added. Additionally, the
catalyst is tolerant of water and trace amounts of oxygen.
Although other controlled radical polymerization systems
have been reported by various groups, ATRP remains the most
powerful, versatile, simple, and inexpensive. Only ATRP has
been able to polymerize a wide range of monomers including
various styrenes, acrylates and methacrylates as well as
other monomers such as acrylonitrile, vinyl pyridine, and
dimes. ATRP commonly uses simple alkyl halides as
initiators and simple transition metals (iron, copper) as
the catalysts. These catalysts can be used in very low
amounts, whereas, other controlled polymerization systems
require the use of expensive reagents in much higher
concentrations.
Introduction
Polymeric capsules and hollow particles can be prepared both
from monomeric starting materials as well as from oligomers
and pre-formed polymers.l In most cases, the process involves
a disperse oil phase in an aqueous continuous phase, and the
precipitation of polymeric material at the oil - water
interface causing each oil droplet to be enclosed within a
polymeric shell. Interfacial polycondensation is used to
prepare poly (urea) , 11 poly (amide) , or poly (ester) capsules, iii
for instance, by reaction between an oil soluble monomer and
a water soluble monomer at the oil - water interface. On the
3
CA 02387476 2002-05-24
50057-3
other hand, vinyl polymers such as poly(styrene), acrylates
and methacrylates prepared by free radical polymerization
under suspensionl° or emulsion polymerization°~°i
conditions
have been used to prepare hollow or capsular polymer
particles. In this approach, the dispersed oil phase
usually serves as the polymerization solvent. The oil phase
is chosen so as to be a good solvent for the monomeric
starting materials but a non-solvent for the product
polymer. Therefore, upon polymerization the system is
comprised of three mutually immiscible phases. Over the
past three decades, several groups have studied the factors
governing the morphologies that two immiscible phases can
adopt when they are brought together in a third immiscible
phase by means of a velocity gradient or otherwise. Their
findings have led to an understanding of the morphologies
that result when, for instance, two immiscible polymers are
brought together in a non-solvent for either.
Torza and Mason°ii studied the phase behavior of low
viscosity, immiscible organic liquids dispersed in an
aqueous phase as the drops were subjected to varying shear
and electric fields. They defined the spreading coefficient,
S~ = Y~x - (Y~~ + Yix) . where i , j , and k represent the three
immiscible phases and Y, the interfacial surface tension. For
the premise that, y12 > Yz3, it follows that S1< 0. The
definition of Si, leads to only three possible sets of values
of Si
Sl < 0, S2 < 0, S3 > 0; [1]
Sl < 0, S2 < 0, S3 < 0; [2]
Sz < 0, S2 > 0, S3 > 0; [3]
4
CA 02387476 2002-05-24
50057-3
It was shown that for interfacial conditions of equation [1]
the core-shell morphology is preferred, while for equation
[2] the hemispherical morphology is preferred. Good
agreement was found between the theoretical predictions and
experimental results. It is noteworthy, that Torza and Mason
used low viscosity oils that are able to diffuse rapidly and
assume the lowest interfacial energy morphology within the
time frame of the experiment. Sundberg et.al."iii published a
theoretical model based on the Gibbs free energy change of
the process of morphology development. Starting with three
immiscible phases; oil, polymer and water, they showed that
the Gibbs free energy change per unit area for the process
leading to a core shell morphology (with oil encapsulated
within the polymer phase), is given by:
0G = yop + YpW ( 1 - ~P ) -2/3
Where yoP, ypW, and yow are the oil-polymer, polymer-water and
oil-water interfacial tensions and ~p is the volume fraction
of the polymer (in polymer plus oil "combined phase"). In
the limit as ~p tends to zero, equation [4] reduces to,
2 0 0G = ('Yop + 'Yp,N ) - 'Yow [ 5 ]
Thus, when yoW > (yop + ypW) [6] , the core shell morphology with
the core oil being engulfed by the polymer is the
thermodynamically stable morphology. Analogous expressions
were derived for the hemispherical, inverse core shell and
distinct particle morphologies. Using these expressions the
authors were able to predict the expected morphologies for a
given set of interfacial conditions. The predictions were
checked and confirmed by experiment.
5
CA 02387476 2002-05-24
50057-3
In an earlier work, Berg et. al.lX showed the above analysis
is equally valid when the polymer is synthesized in situ by
free radical polymerization. Poly(methyl methacrylate) was
prepared via free radical polymerization by dispersing n-
decane or hexadecane, methyl methacrylate and an oil soluble
initiator in water containing a surfactant or stabilizer. It
was shown that the resultant morphology was critically
dependent on the type of emulsifier used. The authors
concluded that this observation appeared to be related to
the minimization of interfacial energy for the particles as
they are dispersed in water. In summary, the particle
morphology that results from in situ polymer synthesis in
suspension/emulsion polymerization conditions is
predominantly driven by interfacial energy criteria.
The work of the four major research groups in the area,
i.e., Kasai et. al., Okubo et. al., McDonald et. al., and
Sundberg et. al., shows that present techniques allow only
the encapsulation of relatively hydrophobic solvents.
McDonald et. al. and Sundberg et. al. have encapsulated
highly non-polar core oils such as decane and octane. Kasai
et. a1. and Okubo et. al. have encapsulated slightly more
polar materials such as benzene, toluene and xylene. Since
these groups set out to synthesize hollow polymer particles,
the nature of the core oil does has not been of relevance.
However, if core-shell particles are intended for
encapsulation of the core material, then it becomes
desirable that the technique allows encapsulation of both
hydrophobic and hydrophilic core materials.
Core-shell particles, with polymer engulfing an oil core,,
only form if the sum of the oil/polymer and polymer/water
interfacial tensions is less than the oil/water interfacial
tension. Consequently, encapsulation of more hydrophilic
6
CA 02387476 2002-05-24
50057-3
material demands the ability to synthesize sufficiently
amphiphilic polymers that will satisfy this interfacial
requirement. Copolymers comprised of an oil-soluble and a
water-soluble monomer are amphiphilic materials whose
polarity characteristics can be conveniently controlled by
varying the comonomer ratios. However, the synthesis of
these materials in suspension polymerization conditions :is
non-trivial since the water-soluble monomer partitions into
the aqueous phase and is only partially incorporated into
polymer forming in the oil phase if conventional free
radical polymerization is used as the means of polymer
synthesis. We propose that the use of a living
polymerization method as the means of polymer synthesis will
allow the preparation of amphiphilic copolymers by
suspension polymerization. Provided these copolymers are
sufficiently amphiphilic they should, in principle, meet the
interfacial requirement for encapsulating more hydrophilic
core oils.
We describe herein, the in situ synthesis of an amphiphilic
co-polymer designed to migrate to the oil-water interface
and thereto crosslink and precipitate. The amphiphilic
copolymer, poly(methyl methacrylate-co-poly(ethylene glycol
monomethyl ether) methacrylate)), was prepared by atom
transfer radical polymerization (ATRP) in suspension
polymerization conditions. ATRP being a living radical
polymerizationX-Xi ensures that all polymer chains remain
active and that the water-soluble co-monomer (poly(ethylene
glycol methacrylate)) is incorporated continuously into each
polymer chain throughout the suspension polymerization. This
is essential to impart the desired amphiphilic nature to the
copolymer. ATRP is tolerant to water or other protic
solvents and impurities unlike ionic living polymerization
7
CA 02387476 2002-05-24
50057-3
methods and proceeds efficiently at temperatures below the
boiling point of water making it the method of choice for
aqueous suspension polymerizations.Xii In addition, this work
opens the possibility of building capsular walls from block
and terpolymers in future.
The invention may be used to encapsulate very polar
materials such as pharmaceutically active materials,
dissolved in a polar solvent such as glyceryl triacetate
that is suspended in a hydrophobic continuous phase, wherein
the continuous phase could be a linear or cycloaliphatic or
aromatic solvent ranging from C5 through C20.
This would permit use of many biocompatible monomers such as
hydroxyethylmethacrylate and methacrylamide as wall forming
monomers at room temperature, using the very active linear
amines based on oligomers of ethyleneimines, ranging from 2
through 50 repeat units of ethylene imine.
A key aspect of the invention is that the copolymerization
of the alkylmethacrylate or acrylate and the
polyalkyleneglycol methacrylate or acrylate, can be carried
out initially in a homogeneous solution and to different
degrees of conversion or chain length. Subsequently, as
crosslinking monomers is added and the reaction mixtures in
transferred into the suspension polymerization reactor,
different morphologies are observed. For example, reaction
mixtures transferred at high conversion will a more capsular
morphology, with dense walls, while reaction mixtures
transferred at lower conversion in the initial
copolymerization will result in final particles showing more
homogeneous distribution of polymer throughout the capsule,
as in a matrix particle.
8
CA 02387476 2002-05-24
50057-3
In other words, ATRP provides the ability to control the
polymer solubility in a given core solvent, by controlling
the degree of conversion, and hence the length of the living
copolymer chains, at which the crosslinker is added and the
polymerization mixture is transferred into the suspension
reactor. Thus for a given ratio of the comonomers, we are
able to tune the morphology via the polymer architecture
ie., molecular weight of linear polymer chains on the
crosslinked polymer. This morphology in turn can control the
release behavior of the active materials inside the
capsules.
Results and Discussion
Copolymer synthesis in Biphenyl ether. The ATRP synthesis of
poly(methyl methacrylate-co-poly(ethylene glycol monomethyl
ether) methacrylate)) (PMMA-co-PegMA) was first developed in
solution polymerization conditions. A series of copolymers
comprised of methyl methacrylate (MMA) and 9.5, 18, 39, and
60 mol% polyethylene glycol monomethyl ether) methacrylate
(PegMA) were prepared by both solution and suspension
polymerization. biphenyl ether (DPE) was used as solvent
since it is a relatively polar solvent as reflected by it=s
solubility parameter (Table 1). Furthermore, it is a good
ATRP solvent owing to its low chain transfer constant and
its use for the ATRP of methacrylate monomers has been
reported."iil Toluene sulfonyl chloride (TSC) was used as
initiator and a catalyst based on Cu(I)Br and 4,4'-dinonyl-
2,2'-bipyridine (dNBpy) was used as ATRP catalyst. The
modified bipyridine ligand ensures homogeneous catalyst
solubility in Biphenyl ether as well as favorable
partitioning of the catalyst into the oil phase during
9
CA 02387476 2002-05-24
50057-3
suspension polymerizations,Xi" Both the solution
polymerizations and the suspension polymerizations were run
at 70 °C. The aim here was to develop the ATRP synthesis of
PMMA-co-PegMA for use in the encapsulation reaction and thus
preparation of the copolymer at low monomer loadings (10 -
50 % w / w) was desirable. The range of interest from the
encapsulation view point is between 10 and 25 weight percent
as this amount of polymer is sufficient for constructing the
capsular wall. For development of the ATRP reaction we chose
a monomer feed composition of 82 mol$ MMA and 18 mold PegMA.
Other water immiscible solvents besides diphenyl ether may
include alkyl acetates, alkyl propionates, alkyl butanoates,
alkyl adipates, alkyl benzoates, and alkyl phthalates, in
each case with alkyl chains ranging from C1 through C12.
Additionally, industrially used plastizicers such as acetyl
trialkyl citrate, with alkyl chains ranging from C2 through
C6 can be used. Aliphatic alcohols ranging from C4 through
C12, dialkyl ketones with the sum of both alkyl groups
ranging from C4 through C20, and dialkyl ethers with the sum
of both alkyl groups ranging from 4 through 20 are suitable
solvents.
As seen in Table 2, all ATRP reactions exhibited final
polydispersity of 1.1-1.2 as well as good agreement between
the theoretical and experimental number average molecular
weights (Mn). The experimental molecular weight (Mn (SEC)),
increased linearly with conversion, while the
polydispersities showed a slight increase with conversion
(Figures 1 and 2). Figure 3 indicates that the reaction
rate was first order in monomer concentration indicating
that the free radical concentration remained constant
throughout the reaction period for all cases.
CA 02387476 2002-05-24
50057-3
Furthermore, it is noteworthy that the reaction rate
increases from 10 through 25% monomer loading and drops
again at 50% loading. From the ATRP rate equation,
Rp = kp(ka/kd) [M] [Cu(I)] / [Cu(II)X]
it is evident that the rate of polymerization, Rp, depends on
the propagation rate constant, kP, the activation /
deactivation constants of the propagating radical, ka/kd, as
well as the monomer concentration, [M], and the relative
concentrations of the Cu(I) and Cu(II) species, [Cu(I)] /
[Cu(II)X]. Explanation of the observed rate dependence on
monomer loading apparently lies in the manner in which kp,
ka/kd, and [Cu ( I ) ] / [Cu ( II ) X] respond to monomer loading . No
further experiments were performed to determine how these
parameters) vary with monomer loading.
Results of the ATRP synthesis of the copolymers
containing 9.5, 39, and 60 mol% PegMA are shown in Figures
4, 5 and 6. Polymerizations proceeded to high conversions in
each case and polydispersity remained low confirming the
living character of the polymerization. We attribute the
difference between the experimental molecular weight
(Mn(SEC)) and the theoretical molecular weight (Mn(Theo)) to
structural differences between the GPC calibration standard
i.e. poly(styrene), and the copolymer. Apparently, the over
estimation of molecular weight increases with the amount of
PegMA in the copolymer as can be seen in Figure 4.
Copolymer synthesis in suspension conditions. Next, the
ATRP synthesis of PMMA-co-PegMA was performed, in part, in
suspension conditions. The purpose of this experiment was
two fold. First, to show that PMMA-co-PegMA can be prepared
by ATRP in suspension polymerization conditions. Secondly,
to prove that the composition of the formed copolymer would
11
CA 02387476 2002-05-24
50057-3
reflect the comonomer ratios in the feed. PMMA-co-PegMA
containing 18 mol% PegMA was chosen for this experiment. The
copolymer synthesis was initiated in diphenyl ether in
solution conditions and allowed to proceed to a number
average molecular weight of about 5000 Da, corresponding to
about 50% conversion. At this point, the solution
polymerization mixture was transferred to a four-fold excess
of water (by volume) and mechanically stirred at 1000 rpm
for 30 minutes and at 500 rpm thereafter yielding an oil in
water suspension.
Results of the suspension reaction for 25% monomer loading
are presented in Figure 7 and 8. Figure 7 shows time-
conversion curves. The plot of In ([Mo] / [Mt]) versus time
is non-linear above 80% conversion. This may be attributed
to slow diffusion of the water soluble macromonomer back
into the oil phase rather than to irreversible termination
reactions such as recombination of growing radicals. Slow
diffusion would cause the total monomer concentration in the
oil phase to be lower than if neither monomer would
partition into the aqueous phase. Hence, at high conversion
i.e., low (instantaneous) monomer concentration, the
propagation kinetics can switch form a reaction control to a
diffusion control. A similar observation was made in the
solution ATRP of the macromonomer polyvinyl ether)
methacrylateX° where the increasing viscosity of the
polymerization medium limits access of the growing polymer
chains to the slow-diffusing macromonomers. Figure 8 shows
that the molecular weight increased linearly with conversion
and that polydispersity remained below 1.2, suggesting good
living character. Hence, the ATRP synthesis of the
amphiphilic copolymer was achieved (with over 80% monomer
conversion) in suspension polymerization conditions.
12
CA 02387476 2002-05-24
50057-3
In order to confirm that the water soluble
comonomer, PegMA, is incorporated in the growing polymer
chains in the oil phase during the course of the suspension
polymerization, NMR spectra of samples taken prior to,
during and the at the end of the suspension polymerization
were recorded. 1H NMR did not permit determination of the
comonomer ratio in the copolymer due to overlap of
potentially useful peaks in the spectrum. Figure 9 shows the
carbon-13 spectrum and the J-modulated spin sort spectrum.
The spin sort experiment helps to pin point the methoxy
carbon resonances in the copolymer. Methoxy of MMA comonomer
was assigned to S~ = 51.9 ppm, while that of the PegMA
comonomer was assigned to 8~ = 59.2 ppm based on the expected
chemical shift values. Figure 10 shows the spectrum of a
sample drawn just prior to transferring the organic reaction
mixture to the aqueous phase and those of samples drawn 1
and 2 hours into the suspension polymerization. Also shown
is the spectrum of a sample of the copolymer prepared by
solution polymerization (conversion = 100 ~). Integration of
the relevant peaks yielded 12% PegMA content in all of the
spectra. The monomer feed in both the solution and
suspension polymerizations contained 18.8 % PegMA. Since the
solution polymerization had proceeded to quantitative
conversion it is reasonable to assume that NMR has
underestimated the PegMA content in the samples. Since
sensitivity of the methoxy carbons may vary due to
differences in the spin lattice relaxation times, the
experiments were repeated in the presence of a paramagnetic
relaxation agent, cr(acac)3. The spectra from this experiment
(Figure 11) yield a PegMA content of 14% in both the
solution polymerization and suspension polymerization
samples. Since, the spectra with cr(acac)3 also showed a
PegMA content lower
13
CA 02387476 2002-05-24
50057-3
than anticipated, a gated decoupling experiment was run to
reduce possible enhancement of the MMA methoxy carbon due to
Nuclear Overhauser Effect. The spectra in Figure 12 yield a
PegMA content of 17 % for both the solution polymerization
and suspension polymerization samples. This confirms that
PegMA was indeed incorporated into the copolymer to the same
extent in the suspension polymerization as it was in the
solution polymerization.
The aqueous suspension, when viewed under an optical
microscope, showed colloidally stable oil droplets with no
tendency to coagulate. Since no surfactant or stabilizer was
used in this suspension polymerization, this suggests that
the amphiphilic copolymer resides at the oil-water interface
thereby stabilizing it.
Encapsulation of Biphenyl ether. The encapsulation process
consisted of three steps: synthesis of low molecular weight
amphiphilic copolymers by solution ATRP; addition of the
cross-linking monomer to the reaction solution followed by a
10 minute mixing period to ensure homogeneous distribution
of the crosslinking monomer; and transfer of this oil phase
to four times excess of 1% aqueous polyvinyl alcohol) (PVA)
in a baffled reactor. The resulting suspension was
mechanically stirred with a propeller type mixer at 1000 rpm
for 30 minutes and subsequently at 500 rpm to the end of
suspension polymerization. The PVA serves as a suspension
stabilizer. A series of encapsulation experiments were
performed to study the effect of the polymer composition on
the internal morphology of the resultant polymer particles.
Table 3 gives details of these formulations. In entries 1 -
5 the total polymer loading in the oil phase and the mole %
crosslinker were held constant while the mole % water
soluble monomer was varied from 0 - 31 mol %. The total
14
CA 02387476 2002-05-24
50057-3
polymer loading in the oil phase was held constant at 30~4 %
(w/w) so that differences in particle morphology at a given
conversion to polymer can be related directly to the
interfacial properties of the forming polymer in the oil
phase. Figures 13 shows an Environmental Scanning Electron
Micrograph (ESEM) of the suspension polymer particles PegMA-
15. The ESEM image showed that while most polymer partic_Les
maintained their spherical shape some were deflated and
assumed a red blood cell like shape under the high vacuum in
an ESEM sample preparation step. This suggests that the
polymer particles have a hollow or less dense interior and a
dense surface shell. Transmission Electron Microscopy (TEM)
was conducted to determine the internal morphology of the
particles. Since conversion is relatively slow in ATRP
reactions, we have observed that the morphology of the
particles develops over time during the encapsulation
reaction. This observation and a full interpretation of it
are intended to be the subject of a future paper. Since
morphology develops with conversion, comparisons are valid
only between particles from reactions that have proceeded to
a similar conversion. Figure 14 -18 show the internal
morphology of particles at 80 - 100 % (w/w) conversion for a
series of polymer compositions. A clear transition in the
internal morphology from matrix particles to hollow core-
shell type particles is observable. The TEM images chosen
represent the predominant morphology exhibited by the
particular particles in question. In all the cases discussed
below, a small minority of the particles possesses
morphologies other than those shown. PegMA-0 particles
exhibit a matrix morphology with a microporous interior and
a denser outer skin at 82% conversion (Figure 14A). At 99%
conversion the density of the interior increases and the
microporous structure disappears as the forming polymer
CA 02387476 2002-05-24
50057-3
occupies the pores (Figure 14B). This suggests that
crosslinked PMMA has a weak tendency to migrate to the oil
water interface as it precipitates from DPE. The PegMA-8
particles at 83% conversion have a macroporous interior and
a more distinct dense polymer wall in the interfacial
region, at 98% conversion the pores are filled by newly
formed polymer (Figure 15A, 15B). The PegMA-15 particles
exhibit a macroporous interior even at 98% conversion
suggesting that the terpolymer has an increasing tendency to
migrate to the oil-water interface with increasing fraction
of PegMA in the composition (Figure 16). In this case, the
crosslinked terpolymer fills the entire volume of the
suspension polymer particles, however, a macroporous
interior characterized by internal voids and a relatively
high density surface skin are observable. This morphology
suggests that some amphiphilic terpolymer migrates to the
oil water interface; the rest remains kinetically and
enthalpically trapped in the interior of the particle to
form a lower density matrix. Upon further increasing the
PegMA content to 31 mol% (PegMA-31) the particles exhibit a
matrix morphology characterized by large internal voids at
92 % (w/w) conversion (Figures 17A). At 98% conversion the
particle morphology develops from that of Figure 19 to
particles characterized by a distinct thin walled capsular
structure as seen in Figure 17B. While Figure 17 shows t:he
predominant morphologies observed for this polymer
composition, a significant minority of particles exhibited a
range of morphologies represented by Figure 18. The tread
toward hollow capsular particles with increasing PegMA
content is easily discernible.
To study the effect of having used a living polymerization,
an experiment using conventional free radical polymerization
16
CA 02387476 2002-05-24
50057-3
was conducted. A monomer feed containing 35 mol% PegMA, 11
mol% DegDMA and 54 mol% MMA was polymerized under suspension
polymerization conditions using benzoyl peroxide as a
thermal initiator at 70 °C. In this experiment, initiator,
monomers and solvent were mixed at room temperature and
degassed by a stream of Argon for 30 minutes. This oil phase
was then transferred to a four fold excess of 1% aqueous PVA
at 70 °C in a reactor. The suspension was mixed at 1000 rpm
for 30 minutes and at 500 rpm thereafter. For direct
comparison with ATRP particles it would be desirable that
these particles be prepared using 20 mol% crosslinker.
However, colloidal stability of the suspension particles is
lost at 20 mol% DegDMA when particles are prepared by
conventional free radical polymerization (CFRP). Thus, in
order to obtain particles that did not coagulate, a lower
crosslinker concentration was used. In our opinion, this
difference in colloidal stability suggests that the actual
crosslink density of the particles prepared by ATRP is lower
than that expected from the fraction of crosslinker in the
monomer feed. A plausible explanation would be the low
radical concentrations in ATRP polymerizations and the
possible resulting inefficiency in crosslinking. At present,
we do not have direct evidence for this hypothesis. Figure
23 and 24 show the internal morphology of the CFRP particles
at 79 and 97% (w/w) conversion to polymer. The analogous
ATRP particles are the PegMA-31 shown in Figure 19 and 20.
No transition in morphology is observable in the CFRP
particles in going from 79 to 97% conversion. The only
observable change with conversion is the expected increase
in density of the matrix at higher conversion. Thus, there
is a clear difference in morphology between the ATRP
particles and the CFRP particles. We attribute this
difference to the fact that the forming polymer in the CFRP
17
CA 02387476 2002-05-24
50057-3
case is not amphiphilic owing to the partitioning of the
water soluble monomer into the aqueous phase which keeps it
from being incorporated into the growing polymer. There is
therefore no driving force for migration of the polymer to
the oil - water interface causing it to precipitate
uniformly within the entire volume of the oil droplet.
Conclusions
We have shown that the use of a living polymerization
ensures the continued incorporation of a water soluble
comonomer in the synthesis of copolymers comprised of a
water soluble and an oil soluble monomer by suspension
polymerization. This finding has obvious implications for
the synthesis of amphiphilic random copolymers as well as
block copolymers that serve as non-ionic surfactants. We
have applied this concept to the synthesis of crosslinked
particles, where the ability to synthesize amphiphilic
copolymer or terpolymers translates into control over
particle morphology. As reflected by its solubility
parameter, diphenyl ether is a relative polar solvent and
encapsulation of solvents with such high polarity has not:
been reported thus far by the suspension polymerization
technique. We believe that the ability to synthesize
sufficiently polar polymers in the oil phase is the key to
successfully preparing capsular particles. Also, we have
observed interesting differences between the rate and
efficiency of crosslinking reactions by ATRP as compared to
crosslinking by CFRP and we intend to pursue these areas to
further explore the potential for use of ATRP towards
control of particle morphology. The development of particle
morphology with conversion and the overall mechanism of
particle formation by ATRP are the subject of our ongoing
research.
18
CA 02387476 2002-05-24
50057-3
Experimental Section
Materials. Copper (I) bromide, toluene sulfonyl chloride,
4,4'-dinonyl-2,2'-dipyridyl, diphenyl ether and polyvinyl
alcohol) (80% hydrolyzed, Mn = 9000 - 10,000 Da) were
purchased from Aldrich and used as received. Methyl
methacrylate, polyethylene glycol monomethyl ether)
methacrylate (Mn ~ 300 Da) and diethylene glycol
dimethacrylate were obtained from Aldrich and passed over a
basic alumina column to remove inhibitor.
Solution ATRP in diphenyl ether. CuBr, dNBpy, MMA, PegMA,
and DPE were placed in a round bottomed flask in a nitrogen
filled glove bag and closed with a septum. TSC was dissolved
in a portion of MMA in a separate round bottomed flask
inside the glove bag and closed with a glass stopper. The
monomer and catalyst solution was degassed in a stream of
argon for 30 minutes and then transferred to an oil bath at
70 °C. The initiator solution was introduced drop wise over a
10 minute period via a previously degassed syringe to the
monomer and catalyst solution. Samples were drawn
periodically via a previously degassed syringe for Gel
Permeation Chromatography (GPC) and conversion measurements.
GPC samples were prepared by diluting with THF and passing
over a neutral alumina column to remove catalyst. Conversion
was determined gravimetrically by precipitation of samples
in cold (-15 °C) pentane and weighing the polymer
precipitate.
Suspension ATRP. The solution polymerization mixture was
transferred via canula to a 100 mL glass reactor containing
the desired amount of distilled, deionised water (1% PVA, in
case of crosslinking reactions) that had been previously
degassed in a stream of argon for 1 hour.'The reactor was
19
CA 02387476 2002-05-24
50057-3
equipped with appropriate baffles to break the vortex caused
by mixing. The suspension was stirred mechanically at 1000
rpm for 30 minutes and at 500 rpm subsequently until the end
of suspension polymerization using a propeller type mixer.
Aqueous suspension samples for conversion measurement and
GPC analysis were drawn periodically via syringe and freeze
dried to remove water. The samples, now containing solvent
and unreacted monomer, were then dissolved in THF by rolling
the vial gently in a modified hot dog roller at room
temperature for 24-48h. The THF solutions were precipitated
in pentane, centrifuged, decanted and vacuum dried at 70 °C
to constant weight.
Measurements. Suspension polymerizations were done in a
Buchi Miniclave Drive 100 mL glass reactor. Polymer
molecular weight was determined using a Waters 590
programmable pump connected to Ultrastryragel columns and a
Waters 410 differential refractometer as detector,
tetrahydrofuran as elution solvent (flow rate = 1 mL/min),
and narrow disperse polystyrene standards. The surface and
internal morphologies were determined using Phillips-2020
Environmental Scanning Electron Microscope (ESEM) and a JEOL
1200EX Transmission Electron Microscope (TEM), respectively.
ESEM samples were prepared by depositing dilute aqueous
dispersions of polymer particles on aluminum stubs, drying
at room temperature and sputter coating with a 5 nm layer of
gold. For TEM analysis, polymer particles were embedded in
Spur epoxy resin and microtomed to ~ 100 nm thickness.
Optical microscopy was performed using an Olympus BH-2
microscope, equipped with a Kodak DC 120 Digital Camera. The
NMR spectra were recorded using a 300 MHz Bruker AV-300
Machine.
Image
CA 02387476 2002-05-24
50057-3
Table 1. Solubility characteristics of some organic solvents
Entry Solvent Solubility Solubility of Solubility of
No. parameter / solvent in water in
MPal~2 water / % v/v solvent /
v/v
1 Ethyl 18.2 / 18.6 9 (25 C) 4 (25 C)
acetate
2 n-butyl 17 / 17.4 0.78 (25 C) 2.9 (25 C)
acetate
3 Hexyl 17.3 Insoluble Insoluble
acetate
4 Xylene 18.0 Insoluble Insoluble
Anisole 19.4 Insoluble Insoluble
6 biphenyl 20.9 Insoluble Insoluble
ether
7 Dimethyl 22.1 / 21.9 Insoluble Insoluble
pthalate
22
CA 02387476 2002-05-24
50057-3
Table 2. Synthesis of Poly(MMA-co-PegMA) - 18 mol% PEgMA -
in biphenyl ether at low monomer loading. [MMA] ° . (PegMA] °
[TSC] ° . [Cu (dNBpy) 2Br] ° = 30 : 7 : 1 : 1, 70 °C.
Monomer Conversi Time (h) Mn (SEC) Mn MW/Mn
Concentra on (%) (Theo)
tion (%
w/w)
88 94 10530 8991 1.10
87 12 8068 8891 1.13
88 10 8901 8991 1.16
100 10 10460 10151 1.17
50 94 22 9781 9410 1.16
5
23
CA 02387476 2002-05-24
50057-3
Table 3. Reaction conditions for encapsulation of diphenyl
ether.
Exp. Polym Mole % Mole Conveys Final Conveys
# % Interna
/ er crossli water ion at convey ion to
1
Sample loadi nking solubl transfe sion polymer
particl
Code ng in monomer a r to to of
a
oil (DegDMA monome suspens polyme particl
phase ) r ion (% r (% es morphol
(% (PegMA w/w) w/w) ogy
( % w/w)
w/w) )
(TEM)
1/PegMA 32 20 0 50(?) 100 82 ; Fig.
-p 14, 15
2/PegMA 34 20 8 35 98 83 Fig.
-g 16,17
3/PegMA 33 20 15 57 100 98 Fig. 18
-15
4/PegMA 31 20 31 46 99 92 Fig. 19,
-31 20
5/PegMA 30 20 48 30 85 98 Fig.
-31 21,22
6*/PegM 28 11 35 - 98 79, 97 Fig. 23,
A-35-C 24
* This encapsulation was done by conventional free radical
polymerization.
24
CA 02387476 2002-05-24
50057-3
References:
' Arshady, R. Microspheres, Microcapsules Liposomes 1999, 1, 1461-1732.
" Beestman, G. B.; Deming, J. M. U.5. Patent No. 4, 417, 916, Nov. 29, 1983.
"' Arshady, R. J. Microencapsulation 1989, Vol. 6, No. 1, 13-28.
'" Kasai et. aI.U.S. Patent No. 4, 908, 271, Mar.l3, 1990.
" McDonald et. al. U.S. patent No. 4, 973, 670, Nov. 27, 1990.
"' McDonald, C. J.; Bouck, K. J.;Chaput, A. B.; Stevens, C. J.; Macromolecules
2000, 33,
1593-1605.
"" Torza, S.; Mason, S., G. Journal of Colloid and Interface Science 1970,
Vol. 33, No. l,
67.
""' Sundberg, D. C.; Casassa, A. P.; Pantazopoulos, J.; Muscato, M.R. Journal
of Applied
Polymer Science 1990, 41, 1425.
°' Berg, J.; Sundberg, D.; Kronberg, B. J. Microencapsulation 1989,
Vol. 6, No.3, 327.
" Patten, T. E.; Matyjaszewski, K.; Acc. Chem. Res. 1999, 32, 895-903.
"' Patten, T. E.; Xia, J.; Abernathy, T.; Matyjaszewski, K.; Science 1996,
272, 866-868.
"" Matyjaszewski, K.; Qui, J.; Shipp, D. A.; Gaynor, S. G.; Macromol. Symp.
2000, 155,
15-29.
""' Wang, J.; Grimaud, T.; Matyjaszewski, K.; Macromolecules 1997, 30, 6507-
6512.
'°" Gaynor, S. G.; Qiu, J.; Matyjaszewski, K.; Macromolecules 1998, 31,
5951-5954.
"° Yamada, K.; Miyazaki, M.; Ohno, K.; Fukuda, T.; Minoda,
M.; Macromolecules 1999, 32, 290-293.
CA 02387476 2002-05-24
50057-3
Hollow Polymer Particles by Suspension/Emulsion
Polymerization
Kasai et al.,i.ii have described the production of hollow
polymer particles by both classical suspension and emulsion
polymerizations, and seeded suspension polymerization. In
the classical suspension polymerization method, the oil
phase consisted of an inert solvent, a hydrophobic and a
hydrophilic monomer, a crosslinking monomer and an oil
soluble free radical initiator. The suspension was
stabilized with organic or inorganic stabilizers. This
method yielded hollow polymer particles with a mean size
distribution of about 10 microns and a total monomer
conversion of 98~. It was shown that exclusion of the
hydrophilic monomer from the system yielded porous polymer
particles rather than hollow particles. Also, exclusion of
the crosslinking monomer led to solid particles with no
core-shell structure. Therefore, to obtain the capsular
morphology it is necessary that the formed polymer has both
hydrophobic and hydrophilic content and be crosslinked.
While the authors have not considered the possible
mechanisms that may have led to the core-shell morphology, a
plausible mechanism supported by their results is as
follows. Upon thermal initiation the suspension
polymerization yields terpolymers comprised of the
hydrophobic, hydrophilic and crosslinking monomers. Since,
the hydrophilic monomer partitions into the water phase i.n
suspension polymerization conditions, the early part of the
suspension polymerization would essentially produce
copolymer that is rich in the hydrophobic monomer and the
crosslinking monomer (divinyl benzene (DVB), also
26
CA 02387476 2002-05-24
50057-3
hydrophobic). On the other hand, the latter part of the
polymerization would yield terpolymers rich in the
hydrophilic monomer. Since the reactivity of the second
vinyl group on DVB is lower than that of the first, it is
postulated that the copolymers formed during the early part
of the suspension polymerization will possess unreacted
vinyl groups that will remain available for polymerization
until the latter part of the suspension polymerization.
Hence, the terpolymers polymers formed in the early and late
periods of the suspension polymerization will be covalently
bonded to yield amphiphilic gels. These amphiphilic gels
would migrate to the oil water interface and precipitate as
the crosslinking reaction proceeds, thereby yielding the
core-shell morphology. This hypothetical mechanism partly
explains why the presence of crosslinker is critical to
obtaining the core-shell morphology. Another plausible
reason is based on the fact that, in general, polymer
precipitation at an interface is associated with an entropic
penalty. This is so because of the reduced degrees of
freedom available to polymer at an interface as opposed to
polymer in the bulk phase. This entropic penalty is less
significant for crosslinked polymer than it is for linear
polymer because the former has fewer degrees of freedom t:o
start with. Therefore, crosslinked polymer is more likely to
precipitate at an interface than is linear polymer (other
parameters being identical). In summary, the entropic
advantage of crosslinked polymer for precipitation at an
interface as well as the formation of amphiphilic gels in
the presence of crosslinker may explain the fact that core-
shell particles are obtained only when the forming polymer
is crosslinked.
27
CA 02387476 2002-05-24
50057-3
Particles of sub-micron diameter were achieved using the
emulsion polymerization method. Here, water soluble
initiator and a surfactant were employed with the remainder
of the system being essentially the same as described above.
Like the suspension system, the presence of both hydrophilic
and crosslinking monomer was critical to obtaining hollow
particles.
Seeded suspension polymerization involved the use
of fine non-crosslinked latex particles prepared via
emulsion polymerization in a previous step. It was essential
that low molecular weight polymer (7000 - 10,000 Da) be used
to ensure efficient swelling of the seed particles. The size
and polydispersity of the final hollow polymer particles
were controlled via the seed particles. Using this method
sub-micron to 10 micron monodisperse particles were
prepared. These hollow particles were monodisperse in
comparison to those prepared via suspension polymerization.
In both the emulsion and seeded suspension polymerization
methods, the presence of both hydrophilic and crosslinking
monomer was critical to obtaining hollow particles.
The compositions used in the examples were based on:
Styrene, n-butyl acrylate or butadiene as hydrophobic
monomer;
4-vinyl pyridine, methyl methacrylate, methacrylic acid or
hydroxyethyl methacrylate as hydrophilic monomer;
Divinyl benzene as crosslinking monomer: and
Toluene or benzene as oil phase.
28
CA 02387476 2002-05-24
50057-3
Okubo et. al,iii prepared core-shell poly(divinylbenzene)
(PDVB) particles (~ 10 ~m diameter) containing toluene in
the core and PDVB in the shell by seeded suspension
polymerization. Polystyrene seeds (~ 3 ~m diameter) were
swollen with DVB and toluene using the "Dynamic Swelling
Method" (DSM) that Okubo developed earlieri" for the
preparation of monodisperse homogeneous PDVB particles. :In
DSM, seed latex particles are dispersed in a solution of
toluene, DVB, radical initiator (such as benzoyl peroxide)
and stabilizer in an ethanol/water mixture. Slow addition of
more water to this mixture drives toluene, DVB and the
radical initiator into the seed particles since the
water/ethanol binary solvent becomes increasingly polar and
therefore immiscible with these organic compounds. In
contrast with the conventional swelling method, this
represents an additional force that drives solvent, monomer
and initiator into the seed particles. In the conventional
swelling method, the seed particles, solvent, monomer and
initiator are soluble in the alcohol/water mixture that
serves as the polymerization medium. Hence, the only driving
force for the solvent, monomer and initiator to partition
into the seed particles is the gain in entropy resulting
from mixing of these compounds with the seed polymer. There
is therefore an upper limit to the amount of solvent,
monomer and initiator that will swell the seeds since the
gain in entropy associated with the mixing process becomes
insignificant after some finite degree of swelling.
Consequently, using the conventional swelling method, ~2 ~m
seed particles can be swollen to -5 ~m diameter. Using DSM,
on the other hand, -2 ~m seed particles can give up to -.10
~m swollen particles. Following the swelling process using
DSM, thermal polymerization of the DVB monomer yields core
29
CA 02387476 2002-05-24
50057-3
shell particles with toluene in the core and a PDVB shell.
Okubo et.al.° have shown that polymerization of styrene under
the same seeded polymerization conditions does not yield
hollow particles, i.e., only when the formed polymer is
crosslinked does it precipitates at the interface with water
yielding the core-shell morphology. By observing the
evolution of the particle morphology during the course of
the suspension polymerization, they proposed a mechanism for
the formation of the hollow particles: the formed PDVB
precipitates in the swollen seed particles and is trapped
near the interface based on surface coagulation and
gradually piles up at the inner surface, resulting in a
cross-linked PDVB shell. Okubo et. al.°1 have also shown that
a minimum amount of seed polymer of a minimum molecular
weight is necessary for the formation of the core-shell
structure. The core volume is controllable via the amount:
and nature of the core solvent.Vii Increasing the amount of
core solvent for a given amount of seed particles increased
the core size. Also, using core solvents that differ in
their water solubility, it was shown that solvents with
higher water solubility gave smaller particles with smaller
core volume due to loss of core solvent to the alcohol/water
polymerization medium. Okubo et. al.°iii conducted suspension
polymerizations of DVB in xylene/toluene solutions of
polymers differing in their polarity (as reflected by the:
solubility parameter) (Table 1), and monitored particle
morphology. The polymer solutions in these experiments
represented seed polymer of seeded suspension
polymerizations. The interfacial tension between water and
the polymer solutions determined the observed particle
morphology.
CA 02387476 2002-05-24
50057-3
Table 4. Solubility parameters and Interfacial surface
tensions with water of some polymer solutions.
Seed polymer Solubility parameter Interfacial
/ MPal~2 tension (mN/m) '~
Polystyrene) 18.7 35.0
Poly(n-butyl 17.8 31.7
methacrylate)
Poly(n-butyl 17.4 29.8
acrylate)
Poly(ethyl 18.2 25.5
methacrylate)
Poly(ethyl 19.8 22.4
acrylate)
Poly(methyl 19.3 18.4
methacrylate)
Poly(methyl 20.1 12.9
acrylate)
Interfacial tension (measured by the Du Nouy ring method at
23 ~ 3 °C) between water and Xylene/toluene (l: l, w/w)
solutions of various homopolymers (0.01 wt%).
The interfacial tension between water and xylene/toluene
(1/1, w/w) is 34.8 mN/m and that between water and a 0.01
wt% PDVB solution in xylene/toluene (1/1, w/w) is 29.5 mN/m.
It was observed that when the interfacial tension between
water and the seed polymer solution was below 20 mN/m, no
31
CA 02387476 2002-05-24
50057-3
hollow particles formed. For interfacial tension between 20-
30 mN/m, hollow particles with a rough inner (shell) surface
and an unclear shell structure were observed. Clear hollow
particles were observed only when the interfacial tensions
were above 30 mN/m. Thus, hollow particles formed only when
the PDVB interfacial surface tension with water is below
that of the core polymer solution.
McDonald et. allX,X have also reported the preparation of
hollow latex particles by conventional and seeded emulsion
polymerization. The conventional emulsion system consisted
of an oil phase dispersed in water with the aid of
surfactant. The oil phase contained monomer that is
essentially non-water soluble and a hydrocarbon oil that
dissolves the monomer but is non-solvent for the formed
polymer. The aqueous phase consisted of a water soluble
initiator and a water miscible alcohol.
The seeded emulsion polymerization differed from the above
system in that the seed latex particles were swollen by the
oil phase prior to initiation of the polymerization. The
encapsulation process occurred in two stages. First, a low
molecular weight polymer was made (e. g., 8000 Da using chain
transfer agents). The polymer being insoluble in the
hydrocarbon solvent begins to phase separate and concentrate
at the oil water interface. At this point, a second charge
of crosslinker and monomer were added to the system. The
additional monomer and crosslinker absorb into the surface
polymer phase on the oil droplets. Oligomers from initiation
in the water phase also anchor onto this surface polymer
phase. Thus, the surface polymer layer (on the oil droplets)
now serves as the locus of further polymerization and the
crosslinked network that results stabilizes the surface
polymer layer yielding the hollow particle morphology.
32
CA 02387476 2002-05-24
50057-3
The addition of water miscible alcohol to the water phase
was shown to be critical for efficient encapsulation; in the
absence of alcohol, latex particles with a layer of
hydrocarbon on the surface were obtained. In a model
experiment, increasing the amount of alcohol lowered the
interfacial surface tension between an alcoholic aqueous
phase and an 80/20 mixture of polystyrene) and
ethylbenzene, thereby partially explaining the enhanced
encapsulation efficiency in the presence of alcohol.
Over the past three decades, several groups have studied the
factors governing the morphologies that two immiscible
phases can adopt when they are brought together in a third
immiscible phase by means of a velocity gradient or
otherwise. Their findings have led to an understanding of
the morphologies that result when, for instance, two
immiscible polymers are brought together in a non-solvent
for either. This occurs in a seeded emulsion polymerization
when the formed polymer and seed polymer are in mutual
contact, and are dispersed in an aqueous phase. The same
fundamental principles govern the morphology of composite
particles that result when a polymer, and a non-solvent
organic oil are brought together in an aqueous dispersion,
as is the case during the encapsulation of an organic oil.
Torza and Mason"1 studied the phase behavior of low
viscosity, immiscible organic liquids dispersed in an
aqueous phase as the drops were subjected to varying shear
and electric fields. They defined the spreading coefficient,
Si = yak - (yip + yik) , where i, j , and k represent the three
immiscible phases and y, the interfacial surface tension. For
the premise that, y12 > yz3, it follows that S1< 0. The
33
CA 02387476 2002-05-24
50057-3
definition of Si, leads to only three possible sets of values
o f Si
Si G 0, SZ < 0, S3 > 0; [1]
S1 < 0, S2 < 0, S3 G 0; [2]
SI < 0, SZ > 0, S3 > 0; [3]
It was shown that for interfacial conditions of equation [1]
the core-shell morphology is preferred, while for equation
[2] the hemispherical morphology is preferred. Good
agreement was found between the theoretical predictions and
experimental results. It is noteworthy, that Torza and Mason
used low viscosity oils that are able to diffuse rapidly and
assume the lowest interfacial energy morphology within the
time frame of the experiment. Hence, their results may not
extend to cases when one or more of the components is a high
molecular weight polymer, since diffusional resistance may
prevent equilibrium morphology from being realized during
the experimental time frame.
Sundberg et.al."ii published a theoretical model based on the
Gibbs free energy change of the process of morphology
development. Starting with three immiscible phases; oil,
polymer and water, they showed that the Gibbs free energy
change per unit area for the process leading to a core shell
morphology (with oil encapsulated within the polymer phase),
is given by:
2 5 OG = YoP + YpW ( 1 - ~p ) 2 ~ 3 - Yow [ 4 ]
Where Yop, YpW, and YoW are the oil-polymer, polymer-water and
oil-water interfacial tensions and ~P is the volume fraction
34
CA 02387476 2002-05-24
50057-3
of the polymer (in polymer plus oil "combined phase"). In
the limit as ~P tends to zero, equation [4] reduces to,
DG = ( yop + ypw ) - yoW [ 5 ]
Thus, when yoW > (yoP + ypW) [6] , the core shell morphology with
the core oil being engulfed by the polymer is the
thermodynamically stable morphology. Analogous expressions
were derived for the hemispherical, inverse core shell and
distinct particle morphologies. Using these expressions the
authors were able to predict the expected morphologies for a
given set of interfacial conditions. The predictions were
checked and confirmed by experiment.
In an earlier work, Berg et.al."iii showed the above analysis
is equally valid when the polymer is synthesized in situ by
free radical polymerization. Poly(methyl methacrylate) was
prepared via free radical polymerization by dispersing n~-
decane or hexadecane, methyl methacrylate and an oil soluble
initiator in water containing a surfactant or stabilizer. It
was shown that the resultant morphology was critically
dependent on the type of emulsifier used. The authors
concluded that this observation appeared to be related to
the minimization of interfacial energy for the particles as
they are dispersed in water. It must be stated that the
above model assumes thermodynamic equilibrium and therefore
predicts "final" equilibrium particle morphology. The fact
that it correctly predicts the particle morphology when
polymer is synthesized in situ implies that phase separation
kinetics competes favorably with polymerization kinetics
(under the experimental conditions used by Berg et.al.).
In conclusion, the literature reviewed above suggests that
the particle morphology that results from in situ polymer
CA 02387476 2002-05-24
50057-3
synthesis in suspension/emulsion polymerization conditions
is predominantly driven by interfacial energy criteria. The
work of the four major research groups in the area, i.e.,
Kasai et. al., Okubo et. al., McDonald et. al., and Sundberg
et. al., shows that present techniques allow only the
encapsulation of relatively hydrophobic solvents. McDonald
et. al, and Sundberg et. al. have encapsulated highly non-
polar core oils such as decane and octane. Kasai et. al. and
Okubo et. al. have encapsulated slightly more polar
materials such as benzene, toluene and xylene.
Since the stated objectives so far have been to synthesize
of hollow polymer particles, the nature of the core oil does
has not been of relevance. However, if core-shell particles
are intended for encapsulation of the core material, then it
becomes desirable that the technique allows encapsulation of
both hydrophobic and hydrophilic core materials.
Core-shell particles, with polymer engulfing an oil core,
only form if the sum of the oil/polymer and polymer/water
interfacial tensions is less than the oil/water interfacial
tension. Consequently encapsulation of more hydrophilic
material demands the ability to synthesize sufficiently
amphiphilic polymers that will satisfy this interfacial
requirement. Current techniques that use conventional free
radical polymerization as the means of polymer synthesis do
not permit the in situ synthesis of such amphiphilic
polymers in suspension or emulsion polymerization
conditions. We propose that the use of a living
polymerization method as a means of polymer synthesis will
permit the in situ synthesis of sufficiently amphiphilic
polymers that will meet the interfacial requirement for
encapsulating more hydrophilic materials. The justification
of this proposal is provided in Chapter 2.
36
CA 02387476 2002-05-24
50057-3
References:
Kasai et al., US Patent: 4,908,271 (March 13,1990).
ii Kasai et al., US Patent: 4,798,691 (Jan. 17, 1989).
iii pkubo, M.; Minami, H.; Yamashita, T. Macromol. Symp.
1996, 101, 509-516.
i° Okubo, M.; Shiozaki, M., Tsujihiro, M., Tsukuda, Y.
Colloid Polym. Sci. 1991, 269, 222-226.
" Okubo, M.; Minami, H. Colloid Polym. Sci. 1997, 275, 992-
997.
°i Okubo, M.; Konishi, Y.; Minami, H. Colloid Polym. Sci.
1998, 276, 638-642.
Vii pkubo, M.; Minami, H.; Colloid Polym. Sci. 1996, 274,
433-438.
Viii pkubo, M.; Konishi, Y.; Minami, H. Colloid Polym. Sci.
2000, 278, 659-664.
i" McDonald, C. J.; Bouck, J.; Chaput, A. B. Macromolecules
2000, 33, 1593-1605.
" McDonald et. al., US Patent: 4, 973, 610, Nov. 27, 1990.
"i Torza, S . ; Mason, S . , G. Journal of Colloid and Interface
Science 1970, Vol. 33, No. 1, 67.
Xii Sundberg, D. C.; Casassa, A. P.; Pantazopoulos, J.;
Muscato, M.R. Journal of Applied Polymer Science 1990, 41,
1425.
"iii Berg, J. ; Sundberg, D. ;
Kronberg, B. J.
Microencapsulation 1989, Vol. 6, No.3, 327.
37
