PAPER www.rsc.org/materials | Journal of Materials Chemistry

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Morphology tailoring and temperature sensitivity control of waist cross-linkedmicelles and evaluation of their application as intelligent drug carriers†

Conghui Yuan,a Yiting Xu,a Yifu Liao,a Sujuan Lin,a Ning He*b and Lizong Dai*a

Received 25th June 2010, Accepted 4th August 2010

DOI: 10.1039/c0jm02023k

A novel type of waist cross-linked micelle (WCM) was developed as an intelligent drug carrier via the

self-assembly guiding free radical polymerization of an amphiphilic oligomer: octadecyl, polyethylene

glycol butenedioates (O–B–EGs). By changing the concentration of O–B–EG reaction solution, WCMs

with monolayer, compound and vesicle-like morphologies were obtained. These WCMs showed

controllable temperature responsive properties. DLS and UV-vis analyses indicate that the critical

temperatures at which WCMs show an abrupt change in particle size evidently increases with the

increase in the molecular weight of the PEG chains. Direct switching of the release of pyrene in WCMs

is also realized by a slight change of temperature. Pyrene is released rapidly at the temperatures around

the critical temperature of the WCMs, but a further increase in temperature shuts down the release of

pyrene. More importantly, these WCMs exhibit reversible and rapid pyrene releasing-absorbing

behavior. We suggest that these excellent properties endow WCMs with great potential in drug

encapsulation and controlled release

1 Introduction

Amphiphilic molecules with an evident solubility difference

between the hydrophilic and hydrophobic segments, are known

to self-assemble in aqueous solution into nanoscale structures

such as spherical or cylindrical micelles, or vesicles.1–3 Compared

to small molecular surfactant micelles, polymeric micelles are

normally more stable, because of their remarkably low critical

micellar concentration (CMC) and slow rate of dissociation.4,5

Consequently, polymeric micelles, self-assembled from block

copolymers, with special functionality and variable morphol-

ogies,6,7 have been receiving much attention in many fields such

as dispersant technology,8 nanomaterials synthesis,9–11 and

controlled drug release.12,13

Recently, great interest has been raised in the application of

block copolymer micelles as novel carrier systems in the field of

drug encapsulation. Because the hydrophobic core of the block

copolymer micelles induces a high drug-loading capacity, and the

hydrophilic corona of the block copolymer micelles endows

the drug-carriers with unique deposition characteristics in the

body.14,15 Moreover, functionalized polymeric micelles with

stimuli-responsive properties are even more attractive, as they

are able to sense a signal from the environment and respond by

changing their structures. Accordingly, a large number of

sensitive nano-scaled micelles, including temperature,16–18 pH6,19

aDepartment of Materials Science and Engineering, College of Materials,Xiamen University, Xiamen, 361005, China. E-mail: lzdai@xmu.edu.cn;Fax: +86-592-2183937; Tel: +86-592-2186178bDepartment of Chemical and Biochemical Engineering, College ofChemistry and Chemical Engineering, Xiamen University, Xiamen,361005, China. E-mail: hening@xmu.edu.cn; Fax: +86-592-2184822;Tel: +86-592-2183088

† Electronic supplementary information (ESI) available: Syntheticdetails, 1H NMR spectra, IR spectra, TEM images, SEM images andparticle size characterizations of the resultant products. See DOI:10.1039/c0jm02023k

9968 | J. Mater. Chem., 2010, 20, 9968–9975

and magnetic field20 responsive micelles, have been synthesized

and investigated as drug-carriers. Among these intelligent poly-

meric micelles, temperature sensitive polymeric micelles are the

most interesting because environmental temperature is easily

controlled and adjusted. To date, numerous strategies have been

used to synthesize temperature sensitive micelles. However,

almost all the temperature sensitive micelles that have been

reported were based on poly(N-isopropylacrylamide) (PNI-

PAAm) block copolymers.16–18 The exploitation of new materials

to synthesize temperature sensitive micelles is still insufficient.

As the formation of polymeric micelles is controlled by both

kinetic and thermodynamic factors,21 the variation of external

conditions such as polymer concentration and temperature leads

to a change of micellar structure, or even micelle dissociation and

dissolution.22 To stabilize polymeric micelles, shell cross-

linking23–26 and core cross-linking4,27 are two methods that are

frequently used. However, drawbacks are apparent in these two

methods. First, in the case of the core cross-linking method, the

cross-linked structure endows the micelles with a solid core and

reduces their drug-loading capacity. Second, in the case of the

shell cross-linking method, the shell cross-linking reaction must

be carried out at relatively high dilution in order to avoid

intermicellar cross-linking.26 More importantly, both shell cross-

linked and core cross-linked structures immobilize the polymer

chains to a great extent, and hinders the environmental response

of the micelles. Recently, it is noted that a novel type of stabilized

polymeric micelle with a cross-linked structure located at the

intermediary layer has been developed and used as a stable or

intelligent capsule.28–32 These micelles are generally self-

assembled from triblock or functionalized diblock copolymers.

The cross-linking reactions which are carried out between the

intermediate areas of the copolymers can stabilize the micelles

significantly.

In our previous work,33 we synthesized a novel amphiphilic

oligomer, octadecyl, polyethylene glycol 600 butenedioate

This journal is ª The Royal Society of Chemistry 2010

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(O–B–EG600) using two steps of esterification reaction, and

obtained a kind of waist cross-linked micelle (WCM) via the self-

assembly guiding radical polymerization of O–B–EG600. The

waist cross-linked structure could not only stabilize the micelles

but also endow the micelles with a mobile core and shell. We also

found that both O–B–EG600 micelles and WCMs show signifi-

cant temperature sensitivity. However, the WCMs prepared

from O–B–EG600 are multilayer micelles, because the CMC of

O–B–EG600 is low (about 0.15 mg ml�1), and the polymeriza-

tion of O–B–EG600 is carried out in an O–B–EG600 aqueous

solution with a concentration much higher than the CMC. This

multimolecular layer structure endows the WCMs with a large

diameter and results in a sluggish temperature response.

In this report, we synthesized a series of octadecyl, poly-

ethylene glycol butenedioates (O–B–EG800, O–B–EG1000 and

O–B–EG1500) with CMCs much higher than that of O–B–

EG600, because they were constructed from longer hydrophilic

PEG chains. Our work focused on the control of micellar

morphology and temperature sensitivity of WCMs. The micellar

morphology as an effect of the concentration of O–B–EG in

aqueous solution, and the influence of molecular weight of the

PEG chain on the temperature sensitivity of the WCMs were

investigated in detail. We also used this series of WCMs to

encapsulate pyrene to evaluate their application as temperature

responsive drug carriers, and proposed a drug controlled release

model for these WCMs.

2 Experimental section

2.1 Materials

Maleic anhydride (MA), polyethylene glycol 800 (PEG-800),

polyethylene glycol 1000 (PEG-1000), polyethylene glycol 1500

(PEG-1500), p-toluene sulfonic acid (TSA) and octadecyl alcohol

(OA) were purchased from Aldrich. N,N0-methylene bis(acryla-

mide) (MBA), pyrene, potassium persulfate (K2S2O8) and

methylbenzene were analytical grade and used as received from

Shanghai Chemical Reagent Industry.

2.2 Synthesis

O–B–EG800, O–B–EG1000 and O–B–EG1500 (with molecular

weights of 800, 1000 and 1500, respectively) were synthesized

using maleic anhydride, octadecyl alcohol and polyethylene

glycol via two steps of esterification reactions; WCMs800,

WCMs1000 and WCMs1500 were prepared by the polymeriza-

tion of O–B–EG800, O–B–EG1000 and O–B–EG1500, respec-

tively (see ESI†). To control the morphology of the WCMs, the

concentrations of O–B–EGs in the aqueous solution were

adjusted.

2.3 Characterization

Transmission electron microscopy (TEM) measurements were

performed with a JEM2100 at an acceleration voltage of 200 kV.

To prepare the TEM samples, a small drop of WCM solution

was deposited onto a carbon-coated copper electron microscopy

(EM) grid and then dried under room temperature at atmo-

spheric pressure.

This journal is ª The Royal Society of Chemistry 2010

The particle size of the micelles in aqueous solution was

characterized by dynamic light scattering (DLS) on a ZetaPALS.

For the study of the temperature-dependence of particle size, the

diameters of particles in the samples were measured by DLS at

predetermined temperatures.

The UV transmittance of micelles in aqueous solutions was

measured by UV spectrophotometry (Unico UV/vis 2802PCS,

wavelength: 500 nm) at predetermined temperatures.

To investigate the pyrene controlled release from WCMs,

pyrene was dissolved in the aqueous solution of WCMs. After

stirring over night, the fluorescence emission spectra of pyrene in

WCMs solution were measured by fluorescence spectropho-

tometry on an HITACHI F-7000 at predetermined temperatures

(stimulation slit width: 1 nm, emission slit width: 5 nm, scanning

speed: 60 nm min�1). IE/IM was calculated to elucidate the state of

pyrene in the core of the WCMs as an effect of temperature (IE:

intensity of emission peak at 480 nm; IM: intensity of emission

peak at 273 nm). We also measured the reversible releasing-

absorbing property of the WCMs. WCMs in an aqueous solution

which have encapsulated pyrene were first put into a low

temperature environment, and then quickly transferred into

a high temperature environment. Then the fluorescence emission

spectra of pyrene were measured at specific time intervals. The

reversible releasing-absorbing kinetics of WCMs1000 was

investigated with temperature cycles between 40 �C and 44 �C.

IE/IM was noted at a predetermined time.

3 Results and discussion

O–B–EG800, O–B–EG1000 and O–B–EG1500 were synthesized

via a simple route including two steps of esterification reactions

(Scheme 1A) which could be carried out under facile conditions

with high yields. The so-called pyrene 1 : 3 ratio method34,35 was

used to measure the CMCs of these oligomers. We found that the

CMCs of O–B–EG800, O–B–EG1000 and O–B–EG1500 are

0.28 mg ml�1, 0.36 mg ml�1 and 0.43 mg ml�1, respectively. Thus,

micelles are already formed in O–B–EGs aqueous solution with

a concentration higher than 0.5 mg ml�1, and the polymerization

reaction is carried out within the micelles (Scheme 1B). During

the experimental process, we observed that the concentration of

MBA and K2S2O8 influence the polymerization reaction signifi-

cantly. 0.02–0.08 mg ml�1 of MBA and 0.01–0.04 mg ml�1 of

K2S2O8 lead to the synthesis of well-defined WCMs. As both

MBA and K2S2O8 are water soluble, the polymerization prefers

to initiate in the water phase and forms short growing PMBA

radical chains. Then the PMBA radical chains transfer into the

micelles to initiate the polymerization of O–B–EG. Accordingly,

a lower concentration of either MBA or K2S2O8 inhibits the

polymerization reaction, while a higher concentration results in

the formation of PMBA microgel. 1H NMR spectra of the

WCMs in D2O (Fig. 1S†) only show the peaks of protons asso-

ciated with PEG, whereas all the peaks of protons from octadecyl

alcohol disappear, which indicates that the WCMs are con-

structed from a hydrophobic core and hydrophilic shell in

aqueous solution.36,37

3.1 Microstructure of WCMs

To test the morphology of WCMs, TEM is an intuitive method.

Fig. 1A, B and C show the micellar morphology of WCMs

J. Mater. Chem., 2010, 20, 9968–9975 | 9969

Scheme 1 Synthetic pathways of O–B–EG (A) and WCMs (B).

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synthesized from 0.5 mg ml�1 of O–B–EG800, O–B–EG1000 and

O–B–EG1500, respectively. These micelles exhibit sphere like

morphologies, but the spheres are not regular. The average

diameters of WCMs800, WCMs1000 and WCMs1500 calculated

from 20 particles are 13.6, 16.4 and 20.6 nm, respectively, which

indicates that the particle size of the WCMs increases with the

increasing molecular length of the PEG chain. Moreover, the

diameters of WCMs800, WCMs1000 and WCMs1500 calculated

from the TEM images are approximate to two times of the

molecular lengths of O–B–EG800, O–B–EG1000 and O–B–

EG1500, because the theoretical molecular lengths of O–B–

EG800, O–B–EG1000 and O–B–EG1500 are about 7.2, 8.4 and

11.6 nm, respectively. We conclude that the WCMs are con-

structed of monolayers and the particle size of these monolayer

WCMs can be controlled by the adjustment of the molecular

length of PEG chain.

The morphology of WCMs prepared from 2.0 mg ml�1 of

O–B–EG800, O–B–EG1000 and O–B–EG1500 are shown in

Fig. 1D, E and F, respectively. WCMs800 exhibit a regular

sphere like morphology, while WCMs1000 and WCMs1500

show extremely irregular shapes. The diameters of these WCMs

are much larger than the WCMs synthesized form of 0.5 mg ml�1

O–B–EG solutions. We speculate that the WCMs prepared from

2 mg ml�1 of O–B–EG solutions are compound micelles with

multi-layer structures.

When the concentrations of the O–B–EG aqueous solutions

were 4.0 mg ml�1, we found that the WCMs synthesized from

such a high concentration exhibit an interesting hollow structure

(as shown in Fig. 1G, H and I). In other words, vesicles were

obtained from the polymerization of O–B–EGs at high concen-

tration. However, if the polymerization was not carried out,

compound O–B–EG micelles could only be obtained from a 4.0

9970 | J. Mater. Chem., 2010, 20, 9968–9975

mg ml�1 aqueous solution (see Fig. 4Sa†). To gain a better

understanding of the formation of vesicle-like WCMs, we also

synthesized WCMs from a 3.0 mg ml�1 of O–B–EG solution. As

shown in Fig. 4Sb†, vesicle-like WCMs and compound WCMs

coexist. It is a common view that amphiphilic molecules with

long hydrophilic chains and short hydrophobic chains can only

form star-shaped micelles in selective solvents.38,39 However, our

results give strong evidence that amphiphilic molecules with long

hydrophilic chains and short hydrophobic chains can also form

micelles with variable morphologies such as monolayer micelles,

compound micelles and vesicles. We consider that the

morphology of WCMs is not only decided by the concentration

of O–B–EGs, but also directed by the polymerization process.

The particle sizes of O–B–EG micelles and WCMs with

different molecular weights of PEG chain and variable structures

in aqueous solution were measured by DLS (Fig. 5S†). The

diameters of O–B–EG micelles increase gradually with the

increase in O–B–EG concentration, while the WCMs show a very

slight increase in diameter with increasing micellar concentra-

tion. This is because the WCMs are stabilized by the waist cross-

linked structure. An increase of micellar concentration can only

improve the micellar number per unit volume, but can’t induce

an increase in micellar diameter. Moreover, the particle size

distribution of monolayer WCMs is much narrower than that of

compound WCMs and the vesicle-like WCMs (see in Fig. 6S†).

As the monolayer WCMs are constructed from single molecular

layer, the diameters of the micelles are decided only by the length

of the amphiphilic oligomer. Consequently, the monolayer

WCMs show narrow particle size distribution. However,

compound WCMs and vesicle-like WCMs are constructed from

multi-layers, and the free radical polymerization can not control

the number of layers. As a result, their particle size distributions

This journal is ª The Royal Society of Chemistry 2010

Fig. 1 TEM images of (A) WCMs800, (B) WCMs1000 and (C) WCMs1500 prepared from 0.5 mg ml�1 of O–B–EGs solutions; (D) WCMs800, (E)

WCMs1000 and (F) WCMs1500 synthesized from 2.0 mg ml�1 of O–B–EGs solutions; (G) WCMs800, (H) WCMs1000 and (I) WCMs1500 obtained

from 4.0 mg ml�1 of O–B–EGs solutions.

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are broad. In addition, it can be observed that the particle sizes of

WCMs measured by DLS are larger than those calculated from

Fig. 1. This is because the micelles swell in aqueous solution but

shrink significantly in a dry state.

3.2 Temperature sensitivity of O–B–EG micelles and WCMs

A detailed investigation was carried out to test the temperature

sensitivity of WCMs as an effect of the length of PEG chains and

the micellar structure. As shown in Fig. 2, the diameter and the

UV-transmittance of WCMs800, WCMs1000, WCMs1500

(including monolayer, compound and vesicle-like WCMs) in

aqueous solutions show an abrupt change at �40, 42 and 44 �C

respectively. Whereas, the diameter and the UV-transmittance of

O–B–EG800, O–B–EG1000, O–B–EG1500 micelles in aqueous

solution exhibit an evident break at �37, 38 and 40 �C. These

This journal is ª The Royal Society of Chemistry 2010

results indicate that the critical temperatures at which O–B–EG

micelles and WCMs show an abrupt change in particle size

increases with the increasing molecular weight of the PEG

chains. We attribute this to the higher molecular weight of PEG

chains resulting in more hydrogen bonds being formed between

the PEG chains and water. As the temperature sensitivity of these

micelles is mainly induced by the breaking of hydrogen bonds,33

a greater number of hydrogen bonds leads to an increase in

critical temperature of the micelles. In other words, we can

conclude that the critical temperatures of both O–B–EG micelles

and WCMs could be adjusted via a change in molecular weight of

the PEG chains.

Comparing the temperature sensitive curves of monolayer

WCMs, compound WCMs and vesicle-like WCMs, it is found

that WCMs with different morphologies show the same critical

temperatures, which indicates that the micellar structure exhibits

J. Mater. Chem., 2010, 20, 9968–9975 | 9971

Fig. 2 Temperature responsive properties of O–B–EG micelles (B), monolayer WCMs (O), compound WCMs (>) and vesicle-like WCMs (*) with

different molecular weight of PEG chains; diameter of micelles as an effect of temperature: (A) PEG800, (B) PEG1000, (C) PEG1500; influence of

temperature on the UV-transmittance of micelles in aqueous solution (wavelength: 500 nm): (D) PEG800, (E) PEG1000, (F) PEG1500.

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no influence on the critical temperature of WCMs. We also

measured the shrinking speed of WCMs at temperatures higher

than their critical temperatures. As shown in Fig. 7S†, the

monolayer WCMs and the vesicle-like WCMs exhibit a signifi-

cantly more rapid shrinking speed than the compound WCMs.

This is because the monolayer structure and the hollow structure

of WCMs facilitate the shrinking of micelles, but the solid core

and multi-layer structure endow the compound WCMs with

a sluggish shrinking speed. In addition, it can also be found in

Fig. 2A, B, and C that when the environmental temperature is

higher than the critical temperature, the diameters of the WCMs

change slightly, but the diameters of the O–B–EG micelles

decrease significantly with an increase in temperature. We attri-

bute this to the dissolving of O–B–EG micelles because the

micelles are not stabilized by a cross-linked structure. Accord-

ingly, the WCMs are more stable than O–B–EG micelles, and we

believe that the WCMs are more suitable for drug encapsulation.

3.3 Controlled release of pyrene from WCMs

To investigate the application of WCMs as intelligent drug

carriers, pyrene was encapsulated in WCMs to imitate drug

encapsulation and controlled release. It is well know that when

the distance between two pyrene molecules is too short (less than

0.4 nm), excimers will be formed, and a emission peak at

a wavelength of 480 nm will occur in the fluorescence emission

spectrum of pyrene under an exciting light with a wavelength of

334 nm. Owing to the extremely low solubility of pyrene in water,

the formation of excimers is inhibited. As a result, the emission

peak of excimers at 480 nm can hardly be observed in the fluo-

rescence emission spectrum of pyrene in aqueous solution.

9972 | J. Mater. Chem., 2010, 20, 9968–9975

However, when pyrene is incorporated in the core of amphiphilic

micelles, excimers will be formed because the concentration of

pyrene in the hydrophobic core is significantly higher than that of

pyrene in water. Consequently, the ratio of the emission peak

intensity at 480 nm (IE, from excimer) to the emission peak

intensity at 373 nm (IM, from a single pyrene molecule) reflects

the aggregating state of pyrene molecules; a higher ratio indicates

an evident aggregation of pyrene, whereas a lower ratio suggests

a dilute solution of pyrene.40

We firstly measured the fluorescence emission spectra of

pyrene in monolayer WCMs, compound WCMs and vesicle-like

WCMs. It is found that WCMs with the same morphology show

similar fluorescence emission spectra, though the lengths of the

PEG chains in WCMs are different. We conclude that the length

of the PEG chains has little influence on the aggregation

condition of pyrene that is encapsulated in interior of the

micelles. Consequently, our work focused on the influence of

the morphology of WCMs on the fluorescence emission spectra

of pyrene in interior of the micelles. As shown in Fig. 3A, C and

E, the vesicle-like WCMs1000 shows the most intensive emis-

sion peak at 480 nm, whereas the monolayer WCMs1000

exhibits the weakest emission peak at 480 nm. As a higher

intensity of emission peak at 480 nm indicates a higher

concentration of excimers in the core of the WCMs, we

conclude that the excimeris exhibit the highest concentration in

the core of vesicle-like WCMs, and show the lowest concen-

tration in the core of monolayer WCMs. This is because the

hollow structure of the vesicle-like structure endows the WCMs

with a high pyrene-loading capacity. The aggregation of pyrene

in the core of vesicle-like WCMs results in a high concentration

of excimeris.

This journal is ª The Royal Society of Chemistry 2010

Fig. 3 Influence of temperature on the fluorescence spectra of pyrene in WCMs in aqueous solution: (A) monolayer WCMs1000, (C) compound

WCMs1000 and (E) vesicle-like WCMs1000 ((a): 34 �C, (b): 38 �C, (c): 40 �C, (d): 42 �C, (e): 44 �C, (f): 46 �C, (g): 48 �C, (h):50 �C, (i): 54 �C). IE/IM of the

fluorescence spectra of pyrene in WCMs in aqueous solution as an effect of temperature: (B) monolayer WCMs1000, (D) compound WCMs1000, (F)

vesicle-like WCMs1000.

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According to these fluorescence emission spectra, curves of IE/

IM versus temperature were drawn. As shown in Fig. 3B, D and

F, a sharp decrease of IE/IM at 42 �C can be observed in each

figure. We also tested the fluorescence emission spectra of

WCMs800 and WCMs1500 as an effect of temperature using the

same method. Their IE/IM sharply decreases at temperatures in

accord with the critical temperatures shown in Fig. 2. We

consider that the sharp decrease of IE/IM is induced by the

shrinking of the micelles. Fig. 3B, D and E also show that when

the temperature is a bit higher than the critical temperature,

a rapid increase in IE/IM occurs. This interesting result shows that

the concentration of excimer in the hydrophobic core of WCMs

decreases initially and then increases with the increase of envi-

ronmental temperature. As the excimer is only formed when the

distance between two pyrene molecules is short enough, the

change of the concentration of excimer in the hydrophobic core

of WCMs could be considered to be the change in the pyrene

concentration. Consequently, the sharp decrease of IE/IM

represents a rapid reduction in the concentration of pyrene in the

core of the WCMs, whereas a significant increase of IE/IM indi-

cates an evident increase of the concentration of pyrene.

We propose a model to elucidate this interesting process. As

shown in Scheme 2, when the temperature is lower than the

critical temperatures of the WCMs, the hydrogen bond formed

between PEG chains and water leads to the swelling of the

WCMs, and pyrene is compartmentalised in the core of the

WCMs. As a result, the concentration of pyrene in the hydro-

phobic core of WCMs is much higher than that in water, and

Scheme 2 Pyrene release model of W

This journal is ª The Royal Society of Chemistry 2010

IE/IM has a high value. When the environmental temperature is

approximate to the critical temperature of the WCMs, the

breaking of hydrogen bonds formed between the PEG chains and

water molecules results in the shrinking of WCMs. Conse-

quently, pyrene in the core of WCMs is squeezed out through the

waist cross-linked polymer network of the micelles. Moreover,

the increasing solubility of pyrene in water with the increase of

temperature acts as another driving force that promotes the

transfer of pyrene. As a result, the concentration of pyrene in the

core of WCMs decreases significantly, and the value of IE/IM

shows a sharp decrease at around the critical temperatures.

However, when the temperature increases further, the excessive

shrinking of the WCMs induces the close of the polymeric mesh

in the middle area of the micelles. Accordingly, pyrene in the

core of the WCMs can not transfer to the water. The further

shrinking of the WCMs results in an evident increase in the

concentration of pyrene, and the value of IE/IM increases rapidly.

The waist cross-linked structure makes two outstanding contri-

butions to this controlled release system. First, the mobile cores

and shells endowed by the waist cross-linked structure facilitate

the swelling or shrinking of WCMs. Second, the waist cross-

linked polymer network in the micelles switches the transport of

pyrene in the interior of the WCMs.

To evaluate the reversible releasing–absorbing property of

WCMs, the temperature stimulating pyrene releasing-absorbing

kinetics of WCMs1000 was measured with temperature cycles

between 40 �C and 44 �C. As shown in Fig. 4, a dramatic decrease

or increase of IE/IM between two predetermined temperatures

CMs as an effect of temperature.

J. Mater. Chem., 2010, 20, 9968–9975 | 9973

Fig. 4 Temperature stimulating pyrene releasing–absorbing kinetics of monolayer: WCMs1000 (A), compound WCMs1000 (B) and vesicle-like

WCMs1000 (C).

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implies the reducing or rising of the concentration of pyrene in

the core of the WCMs. This result suggests that pyrene in the

hydrophobic core of the WCMs is released at high temperature

but is resorbed at low temperature. We infer that this recurrent

releasing–absorbing property is induced by the reversible

swelling–shrinking behavior of WCMs. Moreover, it can also be

observed in Fig. 4 that the pyrene releasing or resorbing speed of

the monolayer WCMs1000 and vesicle-like WCMs1000 is much

higher than that of compound WCMs (5 min is required for

monolayer WCMs1000 and vesicle-like WCMs1000 to reach

their equilibrium state, whereas at least 10 min is needed for

compound WCMs1000). We consider that the rapid releasing or

resorbing property of monolayer WCMs1000 and vesicle-like

WCMs1000 is induced by the monolayer and hollow structure,

respectively, but the sluggish releasing or resorbing property of

compound WCMs1000 is caused by the solid structure.

The analysis of Fig. 3 and Fig. 4 also indicates that the vesicle-

like WCMs exhibit both high pyrene-loading capacity and rapid

releasing or resorbing speed. Consequently, we consider that the

vesicle-like WCMs is more suitable for the application of drug

controlled release.

4 Conclusions

Controllable synthesis of WCMs with waist cross-linked struc-

ture was realized via self-assembly guiding free radical poly-

merization of O–B–EGs. Our research indicates that amphiphilic

molecules with a long hydrophilic chain and a short hydrophobic

chain can assemble into not only compound micelles but also

monolayer micelles and vesicles. By changing the concentration

of O–B–EG aqueous solution, monolayer WCMs, compound

WCMs and vesicle-like WCMs were prepared. These WCMs

have controllable temperature sensitivity. The critical tempera-

tures at which WCMs exhibit abrupt change in particle sizes

depend much on the molecular length of PEG chain. For

example, WCMs800, WCMs1000 and WCMs1500 exhibit

excellent temperature sensitivity at around 40, 42 and 44 �C,

respectively. We also investigated the pyrene controlled release of

these series of WCMs to evaluate their application as tempera-

ture responsive drug carrier. All WCMs show evident release of

pyrene when the temperature is approximate to the critical

temperatures. However, the release of pyrene can be shut down

when the temperature is higher than the critical temperatures.

Moreover, the WCMs exhibit excellent reversible and rapid

temperature stimulating pyrene releasing-absorbing property.

Pyrene in aqueous solution is absorbed into the core of WCMs at

9974 | J. Mater. Chem., 2010, 20, 9968–9975

low temperature, but released out at high temperature. We

believe that this controllable release property of the WCMs may

prove to be useful in the application of drug controlled release.

Acknowledgements

This work was supported by the National Natural Science

Foundation of China (50873082, 30700020); Research Fund for

the Doctoral Program of Higher Education (20070384047);

Scientific and Technical Project of Fujian Province of China

(2009J1009).

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