REVIEW www.rsc.org/softmatter | Soft Matter

Rheological and structural aspects on associationof hydrophobically modified polysaccharides

Bo Nystr€om,*a Anna-Lena Kjøniksen,a Neda Beheshti,a Kaizheng Zhua and Kenneth D. Knudsenb

Received 3rd October 2008, Accepted 12th December 2008

First published as an Advance Article on the web 6th February 2009

DOI: 10.1039/b817349d

This review covers recent rheological and structural advances in the interactions between

hydrophobically modified polysaccharides (HMP) and surfactants or cyclodextrin compounds in

aqueous media. Depending on the surfactant concentration, mixtures of HMPs and a surfactant can

form strong associating complexes or disrupted networks at high levels of surfactant addition. By

adding cyclodextrin monomers to semidilute solutions of HMPs, the hydrophobic interactions can

be deactivated and a looser network is formed. For HMPs in the presence of cyclodextrin polymers,

network structures with intriguing morphological and rheological features can be constructed. These

complex fluids are of potential interest in the development of systems for drug delivery formulations.

These rheology modifiers are also of current interest in many other technological applications.

1. Introduction

Polysaccharides are linear or branched polymers made up of

sugar-based units. Since these substances are biocompatible and

biodegradable, they are used in medical and pharmaceutical

applications.1–4 Examples of polysaccharides includes pectin,

chitosan, alginate, carrageenan, cellulose derivatives, and

dextran. These macromolecules are usually easy to dissolve in

water, and if they are hydrophobically modified interesting

associative features can be observed. Due to their propensity to

self-associate in aqueous media because of intra- and intermo-

lecular interactions of the hydrophobic moieties, these polymers

are an exceptional asset as rheology modifiers.5 The hydrophobic

interactions lead to the formation of aggregated complexes and/

or three-dimensional networks (gels) that show great potential

for the entrapment of therapeutic active molecules. In the semi-

Bo Nystr€om is a professor at the

Department of Chemistry,

University of Oslo, Norway. He

received his PhD degree from

the Institute of Physical Chem-

istry, Uppsala University,

Sweden, in 1978 and became

‘‘docent’’ at the same Institute

later. His research activities

focus on structural, dynamical,

and rheological studies of

associating polysaccharides,

hydrogels, microgels, responsive

copolymers, and nanoparticles.

aDepartment of Chemistry, University of Oslo, P.O. Box 1033, Blindern,N-0315, Oslo, NorwaybDepartment of Physics, Institute for Energy Technology, P.O. Box 40,N-2027, Kjeller, Norway

1328 | Soft Matter, 2009, 5, 1328–1339

dilute concentration regime, hydrophobically modified poly-

saccharides (HMPs) frequently exhibit viscosity values that are

several orders of magnitude higher than their precursors.1,5 These

polymers are employed as stabilizers, binders, and thickening or

gelling agents in biomedical, biotechnological, and pharmaceu-

tical applications.

Although hydrophobic interactions promote viscosity

enhancement in solutions of hydrophobically modified poly-

saccharides, it is usually important in many biological systems

and pharmaceutical formulations to be able to tune the strength

of the associations, and this can be accomplished by adding

smaller cosolute molecules such as surfactants or cyclodextrins to

the polymer solutions. In aqueous mixtures of a HMP and

a surfactant, the association strength can be augmented or

weakened depending on the level of surfactant addition.6–10 The

addition of cyclodextrin monomers11 to the polymer solution

provides decoupling of hydrophobic interactions via inclusion

complex formation with the polymer hydrophobic tails, and this

leads to a dramatic reduction of the viscoelastic response.12–23

However, by using cyclodextrin polymers20,23 it is possible to

build up associative network structures. In this case cyclodextrin

Anna-Lena Kjøniksen is

currently a researcher at

University of Oslo; she received

her PhD from the same univer-

sity in 1999. Her research

interests include structural,

dynamical, and rheological

aspects of amphiphilic polymers

in an aqueous environment, and

she has worked on both

biopolymers such as different

polysaccharides, and on various

graft- and block-copolymers.

This journal is ª The Royal Society of Chemistry 2009

cavities of the cyclodextrin polymer encapsulate pendent

hydrophobic tails of the polysaccharide and form bridges

between adjacent polymer chains and thereby, in contrast to

cyclodextrin monomers, strengthen the intermolecular associa-

tions in the system. These uncharged or charged polymers of

cyclodextrin with a branched structure, where the cyclodextrin

units are integrated in the skeleton, constitute another class of

supramolecular assemblies.20,23–26

The present contribution highlights some current activities

toward the understanding of formation of association complexes

in solutions of HMPs and in the presence of surfactants or

cyclodextrin compounds. Since this field is huge and many

publications have appeared over a long period of time, we focus

on recent advances in rheological and structural studies of some

hydrophobically modified polysaccharides in the presence of

various cosolutes. In aqueous media, HMPs exhibit some

remarkable rheological and structural properties that are illus-

trated for some polysaccharide systems in this review. We have

chosen to present results from hydroxyethylcellulose (HEC),

ethyl(hydroxyethyl)cellulose (EHEC), alginate, and dextran, and

from their respective hydrophobically modified analogoues

Neda Beheshti received

a Master degree (2006) from

the University of Oslo, Norway.

She is currently undertaking

a PhD in the Polymer Research

Group of Prof. Bo Nystr€om,

where her research interest is

mainly focused on the ‘‘physical

characterization of interactions

in aqueous solutions of amphi-

philic polymer systems’’.

Kaizheng Zhu received his

chemistry BS degree (1994)

from Hunan Xiangtan Normal

University, and his MS degree in

Physical Chemistry (1997) and

PhD degree in Polymer Chem-

istry (2000) both from the

Chinese Academy of Sciences.

After working as a postdoctoral

fellow in Sun Yat-Sen Univer-

sity, China, he was a visiting

scholar at Aalborg University

(Denmark), Oslo University

(Norway) and Clemson

University (USA). He is

currently a research scientist in Prof. Bo Nystr€om’s group. His

interests include the design and synthesis of water-soluble stimuli-

sensitive block-copolymers by controlled/living radical

polymerization and conjugated polymers with special properties

(photo-electric conversion).

This journal is ª The Royal Society of Chemistry 2009

(HM-HEC, HM-EHEC, HM-alginate, and HM-dextran). The

chemical structures of these polysaccharides are displayed in

Fig. 1. HEC is a nonionic hydrophilic biopolymer with a typical

polysaccharide structure and the hydrophobically modified

analogue (HM-HEC) contains 2 mol% of n-C16H33 groups.

EHEC is a nonionic amphiphilic water-soluble polymer with

hydrophilic and hydrophobic microdomains distributed

randomly along the polymer backbone, and in water the polymer

exhibits a lower critical solution temperature (LCST) (demixing

upon heating). HM-EHEC is a polymer to which low amounts of

hydrophobic side chains (0.73 mol % of C12 and C14 alkyl chains)

have been grafted onto the backbone. Alginate can be charac-

terized as an anionic copolymer, comprising of b-D-mannuronic

acid (M block) and (1/4)-linked a-L-guluronic acid (G block)

units arranged in an irregular blockwise pattern of varying

proportion of GG, MG, and MM blocks. The hydrophobically

modified analogue (HM-alginate) contains 5.4 mol % of

n-octylamine groups or 31 mol % of C8 groups that are grafted

onto the backbone of the alginate chain. Dextran is a nonionic

polymer composed of a-D-(1/6)-linked glucan chains with side

chains that are mostly 1–2 glucose units long and are attached to

the O-3 of the backbone units. In aqueous solution, the branched

nature of the dextran molecules yields a compact molecular

structure. HM-dextran is the hydrophobically modified coun-

terpart that holds 1.6 mol % of glycidyl butyl ether groups.

Although some specific systems have been chosen to elucidate

polymer–surfactant interactions and effects of cyclodextrin or

poly(cyclodextrin) addition, we believe the picture that emerges

from this work provides a general platform for an understanding

of these phenomena in a broad context.

2. Polysaccharide–surfactant interactions

The synergism between hydrophobically modified polymers and

a surfactant has engendered considerable interest over the past

decade. Several studies6,8,10 have shown that the binding of

surfactant to an amphiphilic polymer is cooperative; that is, the

Kenneth D. Knudsen received his

PhD in 1989 from the University

of Trondheim (NTH), Norway,

and after that he worked as

a postdoctoral researcher at

NTH and at the University of

Murcia, Spain. He subsequently

spent several years as

a researcher at the European

Synchrotron Radiation Facility

(ESRF). He is currently senior

scientist at the Institute for

Energy Technology and adjunct

professor at the Norwegian

University for Science and

Technology. His main interests are structural investigations of soft

matter, with particular emphasis on the implementation of neutron

and X-ray methods.

Soft Matter, 2009, 5, 1328–1339 | 1329

Fig. 1 Schematic structures of HM-HEC (x ¼ 0.02), HM-EHEC (x ¼ 0.0073), HM-dextran (x ¼ 0.016), and HM-alginate (x ¼ 0.054).

surfactant molecules form micelle-like aggregates upon binding

to the polymers at the so-called critical aggregation concentra-

tion (CAC), which is independent of polymer concentration and

usually lower than the regular critical micelle concentration in

polymer-free solution. CAC is an important concept in the

description of polymer–surfactant interactions. The binding of

surfactant to the polymer continues until the chains become

‘‘saturated’’, whereafter normal free micelles start to form when

the overall surfactant concentration is sufficiently high.

2.1 Rheological properties

Rheology27 deals with how materials respond to deformation

imposed by the application of a stress onto the sample. The type

of response depends on the state of matter, e.g., liquids will flow

when they are exposed to a stress, whilst elastic solids will be

deformed and they are expected to regain their shape when the

stress is removed. When polymers with hydrophobic stickers

associate and form clusters, it is foreseen that the viscous

and viscoelastic properties are altered, and these changes are

readily monitored in rheological experiments. For this purpose,

1330 | Soft Matter, 2009, 5, 1328–1339

rheology is a powerful method to characterize associations in

polymer solutions.

An added surfactant will interact with the pendant hydro-

phobic groups or hydrophobic micro-domains buried in the

structure of the amphiphilic polymer, leading to a strengthened

association between polymer chains. In the dilute polymer

concentration regime, where the polymer chains act as individual

entities, polymer–surfactant interactions may induce intrachain

aggregation. To illustrate this feature, the effects of surfactant

(sodium dodecyl sulfate (SDS) is an anionic surfactant) addition

and temperature on the intrinsic viscosity [h] for very dilute

aqueous solutions of ethyl(hydroxyethyl)cellulose (EHEC) are

depicted in Fig. 2.28 It should be noted that binding of SDS to

EHEC endows a polyelectrolyte character to the polymer. This

amphiphilic polymer exhibits a lower consolute solution

temperature (LCST) (demixing upon heating), and EHEC

contains mixed hydrophobic and hydrophilic structural units.29

These structural elements are generally unevenly distributed

along the polymer backbone and the substituents are attached

to shorter or longer chains; this favors the development of

a complex structure with an irregular distribution of

This journal is ª The Royal Society of Chemistry 2009

Fig. 2 Effects of surfactant addition and temperature on the intrinsic

viscosity for the EHEC/water/SDS system. Data taken from ref. 28. The

inset plot shows the effect of SDS on the cloud point for 1 wt % EHEC.

Data taken from ref. 29.

Fig. 3 Shear rate dependencies of the viscosity for semidilute aqueous

solutions of HEC, HM-HEC (1 wt%), EHEC (2 wt%), alginate, and

hydrophobic microdomains. The cloud point (CP) for 1 wt%

EHEC solution is 34 �C29 and by adding SDS the value of CP

decreases initially, and at levels of SDS addition above 2 mm†

SDS the value of CP increases monotonically with increasing

SDS concentration (see inset in Fig. 2). This indicates that the

solubility of the polymer is improved at higher levels of SDS

addition, and this may lead to swelling of the polymer entities.

The minimum of the cloud point curve located at approximately

2 mm SDS is ascribed to enhanced polymer–surfactant interac-

tions as the CAC (z2 mm) of the system is approached.

In the dilute concentration regime, the polymer molecules act

as individual units and the intrinsic viscosity is a measure of the

reduced hydrodynamic volume of these species at infinite dilu-

tion, and for flexible coils, the intrinsic viscosity is related to the

radius of gyration Rg and to the hydrodynamic radius Rh

through the relationship30: [h] z Rg2Rh/M, where M is the

molecular weight of the polymer. It is evident from Fig. 2 that at

very low SDS concentrations, the size of the molecules expands

at a given level of SDS addition as the temperature decreases

because the solubility of the polymer increases when the hydro-

phobicity is weakened. The most conspicuous feature is the

strong SDS-induced drop of [h] observed at all temperatures

during the formation of polymer–surfactant complexes. Our

conjecture is that the strong interaction between the hydrophobic

patches of the polymer and the surfactant leads to intramolecular

cross-linking of the coils with contraction of the species as

a result. The onsets of the decreases of [h] are located close to the

CAC values. The minimum of the curve is shifted toward lower

SDS concentration as the temperature rises, and this parallels the

behavior of the temperature effect of the CAC.31 This is ascribed

to the enhanced hydrophobicity of the polymer as the tempera-

ture increases. In this context, it should be mentioned that even in

the absence of surfactant the polymer coils shrink28 with

increasing temperature because of more intense intramolecular

hydrophobic associations.

† Throughout this review, mm ¼ millimolal.

This journal is ª The Royal Society of Chemistry 2009

The pronounced decrease of [h] suggests that the strong

polymer–surfactant association gives rise to a significant collapse

of the polymer–SDS complexes. At higher levels of SDS addi-

tion, [h] rises at all temperatures and this expansion can be

attributed to augmented electrostatic repulsion and excluded-

volume effects due to improved overall solubility of the polymer

as the hydrophobic tails are solubilized.

In a recent theoretical study32 on polymer–surfactant interac-

tions it was argued that in a mixed system of a flexible polymer

and small surfactant molecules the CAC is associated with a local

instability of the polymer chain, and the chain is predicted to

undergo partial collapse around the CAC. It has been specu-

lated33,34 that binding of surfactant molecules to semiflexible

polymer chains (EHEC chains are considered to be semiflexible)

may modify the local stiffness of the chain and this can drive

a partial collapse of the chain.

In semidilute solutions of an amphiphilic polymer in the

presence of a surfactant, a different scenario appears. In this

case, the polymer–surfactant interactions will induce interchain

associations and thereby the transient network is strengthened.

These features can be characterized by rheology, which is

a powerful method to gain insight into the strength of the

network. Shear rate dependence of the viscosity is a common

signature of many associating polymer systems.1,35–37 Effects of

shear rate and SDS addition on the viscosity of semidilute

solutions of HEC, HM-HEC, EHEC, alginate, and HM-alginate

are illustrated in Fig. 3. These examples show the general

viscosity behavior of semidilute solutions of amphiphilic

HM-alginate (1 wt%) at different levels of SDS addition at 25 �C. The

data for alginate and HM-alginate (ref. 36) and EHEC (ref. 35) were

taken from the literature.

Soft Matter, 2009, 5, 1328–1339 | 1331

Fig. 4 Effects of addition of SDS on the zero-shear viscosity (a, b) and

the dynamic viscosity (c) for 1 wt% solutions of HEC, HM-HEC (2 mol%

glycidyl hexadecyl ether groups; n-C16H33), alginate, HM-alginate (5.4

mol% n-octylamine; n-C8), EHEC, and HM-EHEC (mixture of C12 and

C14 alkyl chains grafted to the polymer backbone; 0.73% of the anhy-

droglucose units carries hydrophobic side chains) at 25 �C. Data taken

from refs. 36 and 38.

polymers in the presence of different concentrations of surfac-

tant. At sufficiently low shear rates, Newtonian behavior (the

viscosity is independent of shear rate; zero-shear viscosity) is

observed for all systems. At this stage, the fluid structure is not

much disturbed by the deformation, and then the viscosity

measured during the shear deformation is controlled by the

rates of spontaneous rearrangements, or relaxations present in

the fluid in the virtually quiescent state. Fig. 3 illustrates how the

zero-shear viscosity of hydrophobically modified polymers can

be dramatically enhanced – in some cases more than a 100-fold –

by only moderate amounts of surfactant addition. Note also that

above a certain surfactant concentration, the viscosity starts to

diminish, as will be commented on later. For the HM-alginate

solutions at a low level of surfactant addition (strong interchain

interactions), shear thickening is detected at intermediate shear

rates. This phenomenon suggests a shear-induced reorganization

of the association network, where stretching and alignment of the

chains promote the formation of more polymer–surfactant

junctions. The progressive decrease of the viscosity at higher

shear rates is referred to as shear thinning, and the impact of this

effect is most prominent for the association network with the

highest viscosity enhancement. The shear thinning is attributed

to the breakdown of the network junctions; that is, the rate of

network disruption exceeds the rate at which cross-links are

reformed.

The values of the zero-shear viscosity or the dynamic viscosity

(taken at a low angular frequency) disclose (Fig. 4) strong

polymer–surfactant interactions at moderate surfactant concen-

trations for the hydrophobically modified polymers, whereas no

interaction peak is observed for the unmodified analogues,

except for EHEC. For the EHEC/SDS system, the interaction is

weaker; the peak is broader and the maximum is shifted toward

a higher surfactant concentration. This polymer contains

hydrophobic microdomains and the surfactant molecules can

interact with the hydrophobic moieties, giving rise to viscosity

enhancement. For all solutions of the hydrophobically

modified analogues, viscosity enhancements are observed with

pronounced maxima in the viscosity curves. This behavior indi-

cates the formation of micellar-type cross-links between hydro-

phobic moieties attached on adjacent polymer chains and SDS

(the cross-links are mediated through the surfactant). This results

in a reinforcement of the three-dimensional network, where the

polymer chains are effectively cross-linked by the intermolecular

association complexes of neighboring hydrophobic side chains

and surfactant. In this process, it is generally argued that the

formation of mixed ‘‘micelles’’, consisting of surfactant mole-

cules and hydrophobic tails of the polymer, efficiently raise the

degree of interpolymer association and, consequently, the solu-

tion viscosity. The hypothesis is that the viscosity maxima of the

systems reflect a situation where the ratio between surfactant

molecules and hydrophobic tails or microdomains is optimal for

strengthening the existing network. At a higher level of surfac-

tant addition, a progressive ‘‘solubilization’’ of the hydrophobic

domains occurs, yielding a loosely bound network, and at this

stage the viscosity is low. Interactions between polymer and

surfactant in solution have recently been addressed in theoret-

ical33,39,40 and simulation41 studies. The general hypothesis is that

the hydrophobic moieties of the polymer and hydrophobes on

the surfactant aggregate into mixed micelles that act as cross-link

1332 | Soft Matter, 2009, 5, 1328–1339

junctions in the formation of the associative network. A sche-

matic illustration of the building up and disruption of the

network is displayed in Fig. 5.

2.2 Structural aspects

It has been established over the years that small-angle neutron

scattering (SANS) is a powerful technique to gain insight into

mesoscopic structural changes42–44 of polymer–surfactant

systems with dimensions in the range 10–1000 �A. The scattering

responses result from interferences between neutron rays scat-

tered by different nuclei in the sample. For isotropic samples, the

interferences45 are controlled by the magnitude of the scattering

vector q, which is determined by the wavelength l of the incident

neutrons and the scattering angle q through the expression:

q ¼ (4p/l) sin(q/2).

SANS experiments can be utilized to probe ‘‘local’’ structural

features of polymer–surfactant complexes at different condi-

tions, e.g., effects of temperature and level of surfactant addition.

The impact of temperature and surfactant concentration on the

scattered intensity profile (scattered intensity (I(q)) versus scat-

tering vector) for semidilute aqueous solutions of EHEC without

or with SDS is displayed in Fig.6a–c. In the absence of SDS, the q

dependence of the scattered intensity in the low q regime can be

described by a power-law I(q) � q�a, where the power-law

exponent a reaches the Porod law46 behavior (a ¼ 4) at high

This journal is ª The Royal Society of Chemistry 2009

Fig. 5 A schematic illustration of the surfactant-induced strengthening and disruption of the association network.

temperatures. This trend is in line with the scattering expected45,47

from macroscopic pieces of a dense polymer phase, with sharp

boundaries, in agreement with the high turbidity values (see

Fig. 6d) observed at these temperatures. The turbidity is

a macroscopic phenomenon that is linked to the formation of

large aggregates in the sample. The visual appearance of the

sample at the highest temperature is milky and a macroscopic

phase separation is approached.29 As the surfactant concentra-

tion of the sample increases, the effect of temperature becomes

gradually less palpable and at low q values the scattering curve

flattens out and it follows the Guinier law.48 Actually, at the

highest level of SDS addition the influence of temperature on

the scattering curve is virtually trifling. At a high surfactant

concentration, the hydrophobic microdomains of the polymer

are solubilized to a high degree, the multichain associations are

disrupted by surfactant addition,29 and the impact of tempera-

ture on the scattered intensity is lost. The depression of the

scattering curve in the low q domain and the insignificant influ-

ence of temperature on the scattered intensity are attributed to

better solubility of the polymer and electrostatic repulsive forces

originating from the electrical charges of the surfactant micelles

that are bound to the macromolecules. This scenario of reduced

heterogeneity of the polymer network is consistent with the

turbidity results (cf. Fig. 6d).

Fig. 6 SANS scattered intensity plotted versus scattering vector q at

different temperatures and various levels of SDS addition for the EHEC

(1 wt%)/D2O system. The solid line shows the Porod law (I(q)� q�4). Part

(d) shows the temperature dependences of the turbidity at a heating rate

of 0.2 �C/min. Data taken from ref. 29.

This journal is ª The Royal Society of Chemistry 2009

To further gain insight into structural changes in connection

with interactions between an amphiphilic polymer and a surfac-

tant, SANS results from mixtures of a polysaccharide with

pendant hydrophobic tails (HM-alginate with 5.4 mol% hydro-

phobic groups; n-octylamine groups (C8)) and SDS are shown in

Fig. 7a. For the semidilute HM-alginate solution in the absence

of surfactant, the q dependence of the scattered intensity can be

described by a power-law (I(q) � q�a) over an extended q range.

However, as the level of SDS addition increases a progressive

growing interaction peak in the scattering profile emerges at

intermediate q values. This structure peak accounts for inter-

particle correlations in charged systems and the maxima of the

peaks are located at approximately 0.04 �A�1, which corresponds

to a center-to-center separation of the micelles of about 150 �A

Fig. 7 SANS scattered intensity at 25 �C for 1 wt%HM-alginate plotted

versus the scattering vector at various levels of SDS (a) or deuterated SDS

(b). The dashed line in (a) shows the scattered profile for the SDS(20 mm)/

D2O system without polymer. The inset in (a) shows the effect of SDS

addition on the turbidity. The inset in (b) illustrates the effects of d-SDS

addition on the power-law exponent (I(q) � q�a) in the small q range.

Data taken from ref. 36.

Soft Matter, 2009, 5, 1328–1339 | 1333

(separationz 2p/q). A scattering curve for the surfactant alone,

SDS (20 mm)/D2O solution, is included in Fig. 7a (solid curve).

We notice that for the HM-alginate sample with the same level of

SDS addition a similar profile of the scattered intensity with

a peak maximum located at practically the same q value evolves,

but the peak is less pronounced.

In the light of these findings, it is tempting to suspect that the

scattered intensity from the surfactant gives rise to the structural

peak observed in the polymer–surfactant mixtures. This problem

can be addressed by carrying out SANS experiments on 1 wt%

HM-alginate solutions in the presence of deuterated SDS

(d-SDS) instead of SDS (Fig. 7b). By this procedure, the

measurements are conducted at contrast-matching conditions

where the surfactant is ‘‘invisible’’ in the experiments. It is

interesting to note that in this case no structural peak is visible in

the scattering curves, and this confirms that the peak originates

principally from ionic surfactant micelles and is not a signature

of the polymer structure. The upturn of the scattered intensity

at low q values can be portrayed by a power-law (I(q)� q�a). The

value of a drops with increasing surfactant concentration, and

this behavior is ascribed to deactivation of the hydrophobic

interactions at high levels of d-SDS addition (see the inset of

Fig. 7b). The gradual solubilization of the hydrophobic moieties

leads to fragmentation of the association structures, and this is

reflected in the smaller magnitude of the upturn of the scattered

intensity at low q values. The breakup of association complexes

at high surfactant concentrations is supported by the strong

decrease of the turbidity at high levels of SDS addition (see the

inset of Fig. 7a).

3. Polysaccharide–cyclodextrin interactions

It has been demonstrated above that in solutions of hydro-

phobically modified polymers, addition of an ionic surfactant

can tune the viscosity and structure of the polymer–surfactant

complex. However, changes of hydrophobic interactions modu-

lated through surfactant addition do not provide the specificity

to enable ‘‘triggered’’ alterations in rheology by minor changes in

composition. In addition, a surfactant such as SDS may generate

impediments in the modulation of the system because of elec-

trostatic interactions, and the toxicity of many surfactants make

them unsuitable for medical applications and drug delivery

formulations. To overcome these inconveniences, cyclodextrin

(nontoxic macrocyclic sugars) monomers are well known in

supramolecular chemistry as the most efficient molecular hosts49

capable of encapsulating, with a degree of selectivity, a range of

guest molecules via noncovalent interactions in hydrophobic

cavities. The sequestration of a hydrophobic moiety inside the

cavity of cyclodextrin usually alters the physicochemical prop-

erties of polymer solutions because the hydrophobic stickers are

deactivated. The common cyclodextrin (CD) monomers are

cyclic bracelets formed by 6 (a-CD), 7 (b-CD), or 8 (g-CD) a-1,4-

linked glucose units, with internal hydrophobic cavities of ca.

0.5 to 1.0 nm in diameter.11,50 The 18–24-OH groups are located

on the CD rims, making them soluble in water. The main feature

of cyclodextrin monomers is the cavity that enables them to form

inclusion complexes.

In this review, we elucidate decoupling of hydrophobic

interactions in aqueous semidilute solutions of HM-HEC,

1334 | Soft Matter, 2009, 5, 1328–1339

HM-alginate, and HM-dextran by adding b-CD or hydroxy-

propyl-b-cyclodextrin to the systems. The latter cosolute is used

in some cases to avoid problems with crystallite formation that

may occur in solutions with b-CD at moderate temperatures.51

To gain a more thorough insight into decoupling of hydrophobic

associations with cyclodextrin monomers, results are presented

for hydrophobically modified polysaccharides of various

natures. The addition of an increasing amount of cyclodextrin

monomers leads to a progressive disruption of the associative

polymer network. However, it is also possible to buildup

network structures by means of cyclodextrin, i.e. by using

cyclodextrin polymers, which contain connected multifunctional

cyclodextrin units. In this case we show that polymer networks

can be formed by making bridges between adjacent polymer

chains containing hydrophobic groups. To illustrate this, results

from both an uncharged20 and a charged23 cyclodextrin polymer

are presented, and their structures, together with the structures of

the cyclodextrin monomers, are depicted in Fig. 8. Besides the

chemical structures of the compounds, the architectures of the

monomers and the branched cyclodextrin polymers have been

included. The uncharged b-cyclodextrin polymer (poly(b-CD))

has a weight-average molecular weight Mw ¼ 160 000 and

a polydispersity index Mw/Mn ¼ 1.9. The polymer molecules are

compact because of the branched structure, with a radius of

gyration of Rg ¼ 55 �A, and a b-CD content of 59 wt%.20 The

cationic b-cyclodextrin polymer (poly(b-CDN+)) has an average

of 1.5 positive charges per b-cyclodextrin unit and the weight-

average molecular weight of this sample is Mw ¼ 2.8 � 105, its

polydispersity index is 2.1, its radius of gyration is 19 nm, and its

b-CD content is 54% w/w.23

3.1 Viscosity features

To obtain a detailed picture of the delicate interplay between an

amphiphilic polymer and CD-monomers or CD-polymers,

viscosity is a powerful method to address this issue. Effects of

shear rate on the viscosity for semidilute solutions of hydro-

phobically modified polymers (HM-alginate, HM-HEC, and

HM-dextran) of different nature in the presence b-CD or b-CD

polymers are depicted in Fig. 9. In the case of HM-dextran,

addition of poly(b-CDN+) has only a modest influence on the

viscosity of the solution because dextran is a branched poly-

saccharide and in aqueous solution the molecules are compact. It

is possible that many of the hydrophobic moieties are buried into

the compressed dextran structure, and they are therefore not

easily accessible for the poly(cyclodextrin) cavities. It has previ-

ously been reported12 that addition of b-CD to aqueous solutions

of EHEC has only a slight effect on the hydrophobic effect

because of the bulky hydrophobic patches inside the polymer.

However, if pendant hydrophobic groups are attached to the

EHEC backbone, the viscosity of the solution decreases strongly

upon cyclodextrin addition. In spite of that the concentration

of HM-dextran is high, the viscosity is low and the viscosity

behavior is almost Newtonian. This is another effect of the

compact structure of the polymer and the low sticking

probability of the species.

The general trend for the two other (HM-alginate and HM-

HEC) polymer systems is that increasing concentration of HP-b-

CD lowers the viscosity, whereas the addition of the poly-CDs to

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Fig. 8 Schematic illustrations of b-CD and HP-b-CD with the chemical structure and the truncated cone structure. The chemical structures and the

architecture of the poly(b-CD)20 and poly(b-CDN+)23 polymers are also shown.

the solutions increases the viscosity strongly. In the presence of

poly-CD, some systems exhibit shear thickening at moderate

shear rates and shear thinning at high shear flow. These features

are similar to those observed and discussed for the HMP/

surfactant systems.

To obtain a more detailed picture of the viscosity change,

effects of cosolute addition to the polymer solutions on the zero-

shear viscosity are displayed in Fig. 10. Addition of HP-b-CD or

This journal is ª The Royal Society of Chemistry 2009

cyclodextrin polymers to solutions of unmodified polysaccharide

analogues has no effect on the viscosity behavior. However,

addition of HP-b-CD to polymers with pendant hydrophobic

groups lowers the viscosity significantly for HM-alginate and

HM-HEC, whereas no effect is found for HM-dextran, HP-b-

CD or poly(b-CDN+). This shows that cyclodextrin molecules

encapsulate the hydrophobic tails and thereby gradually

decouple hydrophobic interactions. In this context it is

Soft Matter, 2009, 5, 1328–1339 | 1335

Fig. 9 Shear rate dependences of the viscosity for semidilute solutions of

the indicated hydrophobically modified polymers in the presence of

HP-b-CD or poly(b-CD)/poly(b-CDN+) at 25 �C. Data taken from refs.

20 and 23.

Fig. 10 Comparison of the effects HP-b-CD or poly(b-CD)/poly(b-

CDN+) addition on the zero-shear viscosity of semidilute solutions of the

polymers indicated at 25 �C. Data taken from refs. 20 and 23.

1336 | Soft Matter, 2009, 5, 1328–1339

interesting to note that if b-CD is used instead of HP-b-CD in

solutions of some unmodified polymers (e.g., alginate) at lower

temperatures, crystallites are formed and these act as cross-

linkers; giving rise to a dramatic viscosification of the solu-

tion.20,21 This is an interesting phenomenon but outside the scope

of this review. When a cyclodextrin polymer (poly(b-CD) or

poly(b-CDN+)) is added to a solution of HM-alginate or

HM-HEC, a strong viscosification of the solution occurs and the

polymer network is strengthened because intermolecular bridges

are formed and the number of junction zones increases. A

schematic illustration of the effects of cyclodextrin monomer and

cyclodextrin polymer is shown Fig. 11.

3.2 SANS results

The results presented above have disclosed fundamental differ-

ences in rheological behavior of solutions of hydrophobically

modified polymers in the presence of HP-b-CD or cyclodextrin

polymers. In the light of this finding, it is natural to ask whether

these viscosity alterations are reflected in the structural features

monitored by SANS on a mesoscopic length scale.

Effects of b-CD addition on the scattered SANS intensity

for semidilute solutions (2 wt%) of HM-alginate, HEC, and

HM-HEC are shown in Fig. 12. For the HM-alginate/D2O

system, an upturn of the scattered intensity at low q values is

visible at all levels of b-CD addition, which suggests that struc-

tural inhomogeneities remain in spite of b-CD addition. These

heterogeneities may arise due to hydrophobic interactions and/or

molecular associations. It should be noted that in these studies,

only the tail of the low-q features is observed in the accessible

q-range; therefore precise information about the size of the

clusters cannot be obtained from these data. In this context it is

interesting to note that neither the turbidity results (see the inset

in Fig. 12a) reveal any significant changes upon b-CD addition.

This suggests that not even large-scale associations, probed in

turbidity experiments, are significantly altered at higher b-CD

concentrations.

In the intermediate q-range, where semilocal dimensions of the

polymer are monitored, the scattered intensity varies approxi-

mately as q�1 at all levels of b-CD addition. This type of scat-

tering feature is the signature of linear scattering arrays, as, for

instance, can be anticipated from locally stretched polymers,52

such as alginate that is charged and characterized by a certain

persistence length. The fact that the power law behavior (I� q�1)

of the scattered intensity is not affected by the b-CD concen-

tration indicates that the mesoscopic structural feature is not

influenced by the deactivation of the hydrophobic interactions.

An inspection of the scattered intensity data in the intermediate

q-range divulges that the values of the scattered intensity

decrease to some extent with increasing b-CD concentration.

This probably reflects some degree of decoupling of hydrophobic

associations.

The SANS intensity profiles for 2 wt% solutions of the

uncharged polymers (HEC and HM-HEC) at different levels of

b-CD addition are depicted in Fig. 12b. We note that no effect of

b-CD concentration is found for the solution of HEC, whereas

an upturn of the scattered intensity at low q values is observed for

HM-HEC and this excess upturn is gradually suppressed as the

b-CD addition rises. This is consistent with the picture that the

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Fig. 11 A schematic illustration of the encapsulation of hydrophobic tails in the presence of a cyclodextrin monomer and the formation of inter-

molecular bridges through the encapsulation of hydrophobic stickers on adjacent polymer chains.

Fig. 12 SANS intensity as a function of the scattering vector q at various

b-CD concentrations for 2 wt% solutions of HM-alginate and HEC and

HM-HECat 25 �C.The inset illustrates the effects of b-CDadditionon the

turbidity for alginate and HM-alginate. Data taken from refs. 19 and 21.

Fig. 13 (a) SANS scattered intensity plotted versus scattering vector at

25 �C for 1 wt% HM-alginate in the presence of different concentrations

of the cosolutes HP-b-CD or poly(b-CD). (b) SANS scattered intensity

data from in situ measurements on 1 wt% HM-alginate solution in the

presence of poly(b-CD) (7.9 mm b-CD groups) at the continuous shear

rates indicated at 25 �C. Data taken from ref. 20.

hydrophobic association structures are disrupted with increasing

b-CD addition. This trend is similar to the effects of surfactant

addition to solutions of hydrophobically modified polymers

(cf. the discussion above).

Effects of HP-b-CD or poly(b-CD) addition on the SANS

scattered intensity for solutions of HM-alginate (1 wt%) are

displayed in Fig. 13a. The data for the HM-alginate/HP-b-CD

system demonstrates that the data points virtually collapse onto

each other in the low q-range, whereas at high q-values the curves

clearly separate and the steepness of the tail of the curve is

reduced as the cosolute concentration increases. This finding

suggests that the effect of HP-b-CD addition has little impact on

the large-scale structures but on a more local dimensional scale

structural alterations seem to take place. The trend in the high-q

range may indicate that the polymer chains become less rigid as

the hydrophobic interactions are inhibited.

In the presence of poly(b-CD) the shape of the scattering

curves is practically the same at the considered levels of poly(b-

This journal is ª The Royal Society of Chemistry 2009

CD) addition. There is a shift in the curve toward higher intensity

as the poly(b-CD) concentration rises, but this corresponds to

the change in concentration of the poly(b-CD) itself. However,

we note that when poly(b-CD) is added to the HM-alginate

solution a quite different scattered intensity profile, as compared

with the addition of HP-b-CD, evolves with a ‘‘hump’’ in the

curve at intermediate q-values. This pattern of behavior is

reminiscent of the scattered intensity profile observed for

HM-alginate in the presence of the anionic SDS (cf. Fig. 7). It is

frequently recognized that the structure peak observed in poly-

electrolyte systems accounts for interparticle correlations in

charged systems and it represents structural order. The ‘‘hump’’

may be a harbinger of that ordered structures are formed in the

HM-alginate/poly(b-CD) system.

Since the shear rate dependence of the viscosity for the

HM-alginate/poly(b-CD) system is rather intricate (see Fig. 9),

Soft Matter, 2009, 5, 1328–1339 | 1337

this behavior may be accompanied by structural alterations.

To check this, in situ SANS results on 1 wt% solutions of

HM-alginate in the presence of poly(b-CD) (7.9 mm b-CD

groups) exposed to different shear rates are depicted in Fig. 13b.

The results disclose that all the SANS curves condense onto

a single curve, suggesting that on the mesoscopic dimensional

scale probed in this experiment no structural divergence is

unveiled at the considered shear rates. These results indicate

that no restructuring of the polymer network occurs on the

mesoscopic length scale, but this does not exclude structural

alterations on a global dimensional scale.

4. Conclusions and outlook

In this review we have reported recent advances in the under-

standing of rheological and structural features in aqueous

solutions of hydrophobically modified polysaccharides (HMP) in

the presence of surfactant or cyclodextrin compounds. These

complex fluids or soft materials exhibit special rheological and

structural properties. By adding various amounts of a surfactant

to semidilute solutions of a HMP, the rheological features can

be tuned drastically – from a highly viscous sample to a low-

viscosity solution at high levels of surfactant addition. Various

aspects on polymer–surfactant interactions have been discussed

by using different polysaccharides.

By adding cyclodextrin monomers we have demonstrated that

it is possible to deactivate hydrophobic interactions in solutions

of HMPs in a controlled manner. It has been shown that the

viscosity can be modulated, and this can affect the structural

properties of the solution. New findings have revealed that

addition of cyclodextrin polymers to solutions of HMPs provides

us with a new strategy to connect polymer chains and thereby

build up strong network structures with intriguing architecture

and rheological response.

The use of cyclodextrin monomers in the deactivation of

hydrophobic interactions, and the formation of network struc-

tures by using cyclodextrin polymers in combination with

HMPs offers interesting possibilities in the construction of soft

materials for drug delivery systems. Both HMPs and cyclodex-

trin compounds are biocompatible. Another challenge for the

future is to employ hydrophobically modified polymers in the

presence of cyclodextrin compounds to build up multilayers

adsorbed onto flat surfaces or nanoparticles.

Acknowledgements

We gratefully acknowledge support from the Norwegian

Research Council for the project (177665/V30). NB thanks the

Department of Chemistry, University of Oslo, for financial

support.

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