Dynamics in the Process of Formation of Anisotropic Chitosan

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J. Phys. Chem. B 2010, 114, 10002–10009

Dynamics in the Process of Formation of Anisotropic Chitosan Hydrogel Takao Yamamoto,* Naoko Tomita, Yasuyuki Maki, and Toshiaki Dobashi Department of Chemistry and Chemical Biology, Graduate School of Engineering, Gunma UniVersity, Kiryu, Gunma 376-8515, Japan ReceiVed: March 11, 2010; ReVised Manuscript ReceiVed: June 20, 2010

To control the dynamics of dialysis-induced anisotropic gel formation, we have derived a theoretical expression for the development of the gel layer for a simple case where no cross-link sites for cross-linking agents exists and the inflow and the outflow of low molecular weight components through the dialysis membrane modify the state of polymer molecules to meet the gelation condition. A series of experiments using chitosan solution were done as a model case. The experimental results were compared with asymptotic expressions of the time development equation predicted by theory, and the compatibility of the theoretical picture was examined. 1. Introduction In the case when selective transport through a dialysis membrane results in cross-linkings of polymer molecules, anisotropic gelation occurs.1-5 A typical example is illustrated as follows:6 we pour a concentrated polymer solution such as 2 wt % DNA in borate buffer solution in a dialysis tube and put it into an extradialytic aluminum chloride solution. In the dialysis process, borate flows out and aluminum chloride flows in through the dialysis membrane. Because trivalent aluminum ions can cross-link the DNA molecules, we find a growth of gel from just inside the dialysis membrane to the center. According to the various combinations of intradialytic polymer solutions and extradialytic cross-linking agent solutions, the molecules are known to arrange anisotoropically.1-3,7 Gelation starting from the dialysis membrane can be also regarded as the process when aluminum ions are trapped by DNA molecules to make a gelfront line. In other words, the boundary is formed between the layer where aluminum ions are trapped and the layer where there are no aluminum ions. We call this picture “moving boundary picture”. According to the theory by Yamamoto,8 the dynamic behavior of the dialysis process is “universally” expressed using the gel thickness x and the radius of the dialysis tube R as a function of the dialysis time t as

dx˜ )K dt˜

1 (1 - x˜)ln

1 1 - x˜

(1)

where x˜ ) x/R, ˜t ) t/R2, and K ) A/FG. The system-dependent properties are expressed by the parameter K. Here FG is the cross-linking-agent concentration required for gelation of the polymer solution, and A is a parameter related with the transport phenomena of the crosslinking agent from the extradialytic solution to the polymer solution core. The value of FG is roughly estimated to be proportional to the product of the polymer concentration and the number of polymer cross-linking sites. The transport parameter A depends on the pressure induced by the crosslinking-agent concentration difference between the extradialytic * Corresponding author. E-mail: [email protected].

and the intradialytic solutions. The pressure vanishes when the extradialytic and the intradialytic solutions reach a condition of global thermal equilibrium. Nonequilibirum between the two solutions yields both the ion flow from the intradialytic solution to the extradialytic solution (the outflow) and that from the extradialytic solution into the intradialytic solution (the inflow). The inflow transports the cross-linking agent. The equilibrating process changes the thermodynamic condition of the intradialytic solution. The two parameters FG and A generally depend on the thermodynamic condition of the intradialytic solution. Then, strictly speaking, the knowledge of the thermodynamic condition change of the intradialytic solution during the gelation process and the thermodynamic condition dependence of the two parameters FG and A is required to obtain the solution of eq 1. For gelations of dilute DNA solutions and of carboxymethylcellulose (CMC) solutions,9 the coefficient K could be regarded to be a constant. For these gelations, K is insensitive to the thermodynamic condition of the core solution and the solution of eq 1 is simply given by

y˜(x˜) ) Kt˜ 1 1 1 y˜(x˜) ) (1 - x˜)2 ln(1 - x˜) - x˜2 + x˜ 2 4 2

(2)

Equation 2 gives the minimal picture for the gelation dynamics by dialysis. Variety is given to the gelation dynamics by the dependence of K on the thermodynamic condition of the core solution.9,10 The thermal condition change modifies the conformation and/or the degree of ionization of polymer molecules. These modifications may alter the number of the polymer cross-linking sites. Then, the value of FG changes during the dialysis process, since the value depends on the state of the polymer and the FG change gives various types of gels. However, no further information of the polymer-state dependence of FG for the cross-linking gelation system could have been derived from experimental results; therefore, we could not control the dynamics. Our idea to give controlled variety to the minimal picture is to use a simpler system where no cross-link sites for crosslinking-agents exist and the inflow and the outflow modify the state of polymer molecules to meet the gelation condition. For

10.1021/jp102207w  2010 American Chemical Society Published on Web 07/21/2010

Formation of Anisotropic Chitosan Hydrogel

J. Phys. Chem. B, Vol. 114, No. 31, 2010 10003

FG ) FG(t) ) RC(t)

(3)

where R is a positive constant. According to ref 8, the time development equation of x(t) due to the inflow of NaOH is given by

dx ) K(t) dt

1 (R - x)ln

R R-x

(4)

where

K(t) )

A FG(t)

(5)

Figure 1. Upper view of dialysis system and notation in the theory.

A ) kNaOH(gNaOH(Fs′) - gNaOH(F0′))

(6)

this purpose we chose the gelation of chitosan induced by neutralization as a model case. Chitosan is known to have many useful functions.11-16 Chitosan is also known to have amino groups with positive charges in the range less than pH 6, whereas it has no charge more than pH 6.17 If we dissolve chitosan molecules in acetic acid aqueous solution and put it into a dialysis tube and then dialyze it into sodium hydroxide solution, we have a hydrogel, because the charges are lost and lots of hydrogen-bonding sites in chitosan interact to make a cross-linking network. Therefore, the inflow of sodium hydroxide and the outflow of acetic acid play the role of changing the charges of chitosan molecules to meet the gelation condition, but those molecules do not take part in the cross-linking points. We first develop a theory for this case and then compare it with experimental results.

gNaOH(F′(r)) ) µNaOH(F′(r)) F′(r) - fNaOH(F′(r))

(7)

2. Theory The illustration of the experimental system and the notation is given in Figure 1. The chitosan solution is sandwiched between a set of cover glass with the radius R and immersed into an extradialytic sodium hydroxide solution. F0′, Fs′, F0, and Fs denote the concentrations of sodium hydroxide near the core and near the extradialytic solution in the gel layer, in the core solution, and in the extradialytic solution, respectively. C0′, Cs′, C, and Cs are the concentrations of acetic acid near the core and near the extradialytic solution in the gel layer, in the core solution, and in the extradialytic solution, respectively. r and x(t) denote the distance from the center and the gel thickness at dialysis time t, respectively. In the dialysis process, NaOH flows into the gel layer and acetic acid flows out. Due to the neutralization, the chitosan sol core finally gels. In the dialysis process, Fs is regarded to be constant and Cs is expected to be continuously zero, since the volume of the extradialytic solution is quite large. Since all NaOH flowing into the sol core is used to make the gel layer, F0 is expected to be zero and is independent of the dialysis time. However, C is decreased with the dialysis time by the acetic acid outflow. Local equilibrium is assumed at the interfaces between different layers. Therefore, Fs′, F0′ (≈0), and Cs′ (≈0) are also independent of the dialysis time, but C0′ depends on it. FG is the concentration of hydroxide anions required to make cross-linkings and should be proportional to the acetic acid concentration C(t) in the sol core. Therefore, we have approximately

In the above, the chemical potential of NaOH, µNaOH, in the gel layer is assumed to be a function of the concentration of NaOH at r in the gel, F′(r). The function fNaOH satisfies the equation

∂fNaOH ) µNaOH ∂F′

(8)

The constant kNaOH is the mobility of NaOH. Because of the time independence of Fs′ and F0′, A could be regarded as a constant independent of t. Using the scaled variables

x R ˜t ) t R2 x˜ )

(9)

Equation 4 can be expressed as

dx˜ ) K(t) dt˜

1 (1 - x˜)ln

1 1 - x˜

(10)

Next let us take a consideration of the outflow of acetic acid. The velocity of acetic acid, VAc, is expressed as

VAc ) -kAc

∂µAc ∂r

(11)

where we denote the mobility of acetic acid by kAc and the chemical potential of acetic acid being a function of the concentration of acetic acid C′(r) in the gel by µAc(C′(r)). The flux density vector of acetic acid in the gel is given by

bj Ac ) C′VAcb e r ≡ jAcb er

(12)

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Yamamoto et al.

where b er is the unit vector along the radial direction. At the steady state, we have

div bj Ac )

1 ∂(rjAc) )0 r ∂r

(13)

B r

kAc{gAc(Cs′) - gAc(C0′)} ) -βC

From the eqs 4, 22, and 23, we have the time development expression for the scaled gel thickness x˜ as

(14)

( )

z˜ x˜ ; where the parameter B is independent of r and is determined by the boundary condition given by the local chemical potential equilibrium between the different layers. Equation 14 is rewritten as

∂µAc B kAcC′ ) ∂r r

∫ kAcC′

(15)

R-x

∂µAc R dr ) kAc[gAc(Cs′) - gAc(C0′)]B ln ∂r R-x (16)

∂fAc µAc(C′) ) ∂C′

kAc[gAc(Cs′) - gAc(C0′)] R ln R-x

π(R - x) dC ) -2πRjAc(R) dt

kAc{gAc(Cs′) - gAc(C0′)} R ln R-x

(19)

z˜ ) z˜(x˜ ;h) ≡

∫0

1 1 - x˜ dx˜ 1 - h ln(1 - x˜)

(1 - x˜)ln x˜

(26)

(27) In the small x˜ region, the h ln(1 - x˜) term in the denominator of the integral representation (eq 26) is negligible; for x˜ ≈ 0, the minimal picture z˜(x˜;h) ≈ y˜(x˜) is obtained (the initial stage). In the large x˜ region, z˜ is deviated from y˜ (the late stage). Let us estimate the crossover value of x˜ from the initial stage to the late stage and derivate the dynamics in the late stage. In the integral representation of eq 26, for h ) 2β/Kin, the denominator is expressed as

∆)1-

(20)

2β ln(1 - x˜) ) 1 + ln(1 - x˜)-2β/Kin Kin

(28) The crossover value x˜c is estimated as ln(1 - x˜c)-2β/Kin ) 1. Hence, we have

(21)

x˜c ) 1 - e-Kin/2β

(29)

In the initial stage x˜ , x˜c, the logarithmic term in ∆ is negligible,

Then, eq 20 is rewritten as

kAc{gAc(Cs′) - gAc(C0′)} dC )2 dt R (R - x)2 ln R-x

with Cin ) C(t ) 0) (the initial concentration of acetic acid) and

(18)

Using eqs 14 and 19 we have

RjAc(R) ) -

(25)

1 1 1 z˜(x˜ ;0) ) y˜(x˜) ) (1 - x˜)2 ln(1 - x˜) - x˜2 + x˜ 2 4 2

The flux density, jAc, and the acetic acid concentration in the sol core are related as 2

A A ) RCin FG(t ) 0)

(17)

Therefore, the constant B is expressed as

B)

(24)

The details of the derivation of the above equation are shown in the Appendix. The parameter h characterizes the function z˜ and indicates the deviation from the minimal picture of the gelation dynamics; note that

where corresponding to eqs 7 and 8, we define

gAc(C′) ) µAc(C′)C′ - fAc(C′)

2β ) Kin˜t Kin

where

Kin )

Integrating both sides of the above equation from r ) R - x to r ) R, we have R

(β > 0)

(23)

From the above equation, we have

jAc(r) ) -

Using the ideal gas approximation for the thermodynamic function of acetic acid, we have {gAc(Cs′) - gAc(C0′)} ∝ C. Hence, we put

∆=1

(22) Then,

(30)


( )

z˜ x˜ ;


∫0 x˜(1 - x˜)ln 1 -1 x˜ dx˜ ) 21 (1 - x˜)2

2β ≈ Kin

×

Kin )

1 1 ln(1 - x˜) - x˜2 + x˜ ) y˜ (31) 4 2

Therefore, we have the minimal picture in this region:

z˜ ≈ y˜ ) Kin˜t

(32)

In the late stage 1g x˜ . x˜c, 1 , ln(1 - x˜)-2β/Kin ) -2β/Kin × ln(1 - x˜). Therefore,

∆=-

2β ln(1 - x˜) Kin

(33)

Then, we obtain

( )

2β z˜ x˜ ; ≈ Kin

∫x˜ x c

∫0

(1 - x˜)ln -

(1 - x˜)ln x˜c

1-

1 1 - x˜

2β ln(1 - x˜) Kin

1 1 - x˜

2β ln(1 - x˜) Kin

dx˜ ) a +

dx˜ +

(34)

Kin 1 x˜ - x˜2 2β 2

(

)

γFs RCin

(38)

Hence, Kin is proportional to the ratio of the initial concentration of NaOH in the intradialytic solution and the (initial) concentration of acetic acid in the extradialytic solution. As Kin and β in the time development equation 35 do not include the chitosan concentration, the whole development equation is independent of the chitosan concentration. 3. Experimental Section Chitosan solution was prepared by dissolving chitosan (chitosan 300, the degree of deacetylation >80%, Wako Pure Chemicals) in 0.5-2 wt % acetic acid (acetic acid, analytical grade, Wako Pure Chemicals) at 1-5 wt %. According to the manufacturer, the viscosity coefficient of 5 g/L chitosan in 0.5 wt % acetic acid is 100-500 mPa s. The amount of 89 µL of the chitosan solution was sandwiched between a set of cover glasses with a diameter of 10 mm and immersed into 40 mL of 0.1-1 M sodium hydroxide (Wako Pure Chemicals) dissolved in Milli-Q water in a vial vessel, the temperature of which was controlled at 25 °C in a water bath. By doing so, a cross-linking network is yielded instantaneously at the interface between the inner chitosan solution and the outer sodium hydroxide solution, and the resultant thin gel membrane plays the same role as the dialysis membrane. The solution turned turbid when gelation

Here, the constant a is defined by

( )

a ) z˜ x˜c ;

Kin 2β 1 x˜ - x˜c2 Kin 2β c 2

(

)

(35)

Finally we have, in the range of x˜ . x˜c,

a+

Kin 1 x˜ - x˜2 ) Kin˜t 2β 2

(

)

Rewriting the above equation, we have the asymptotic form in the late stage as

1 x˜ - x˜2 ) 2βt˜ + b 2

(36)

where the slope 2β does not depend on the initial concentration of acetic acid, Cin, and b is a constant. The late stage behavior (eq 36) characterizes the chitosan hydrogel formation dynamics. To compare the above theory with experimental results, let us analyze the parameter Kin. Using the ideal gas approximation for the thermodynamic function of NaOH in the gel layer, we have a simple expression similar to eq 23

A ) γFs

(37)

where γ is a positive constant. From eqs 25 and 37 we have the ideal gas limit expression

Figure 2. The time course of the gel thickness for different concentrations of NaOH at 0.1 M (O), 0.15 M (0), 0.3 M (∆), 0.5 M (3), and 1.0 M (]) in the plot of reduced variables y˜ (a) and x˜ - 1/2x˜2 (b) versus ˜t. The solid lines were drawn according to eqs 32 and 36 for determining the slopes Kin and 2β.

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Figure 3. The parameter Kin (a) and 2β (b) as a function of NaOH concentration Fs. The bars in part b denote the experimental error.

occurred. Therefore, the gel front line was determined from the boundary between the turbid gel layer and the transparent sol core, and these were traced until the gel completion. To examine the dependence of concentrations of NaOH, acetic acid, and chitosan on the dynamics, two concentrations among the three were fixed, and the remaining one was varied. In series 1, the weight percentages of chitosan and acetic acid were fixed at Wchitosan ) 2 wt % and WAc ) 2 wt %, respectively, and the concentration of NaOH was varied in the range CNaOH ) 0.1-1.0 M. We also performed similar experiments at the fixed chitosan concentration of 2 wt % and the sodium hydroxide concentration of 0.3 M with varying concentrations of acetic acid aqueous solution between 1 and 5 wt % (series 2) and at fixed acetic acid concentration of 2 wt % and the sodium hydroxide concentration at 0.3 M with different chitosan concentrations between 0.5 and 2 wt % (series 3). The chitosan concentration range could not be extended further because of a limited viscosity range appropriate both for homogeneous dissolution and for sandwich operation. 4. Results and Discussion Figure 2 shows the time development of the gel layer at various NaOH concentrations in the immersing solution. The behaviors in the initial stage and the late stage were expressed well by linear equations according to eqs 32 and 36, respectively. The slope Kin in the initial stage increases with NaOH concentrations, as shown in Figure 2a. The NaOH concentration dependence of Kin is roughly linear, as shown

Yamamoto et al.

Figure 4. The time course of the gel thickness for different concentrations of acetic acid at 1 wt % (O), 2 wt % (0), 3 wt % (∆), and 5 wt % (3) in the plot of reduced variables y˜ (a) and x˜ - 1/2x˜2 (b) versus ˜t. The solid lines were drawn according to eqs 32 and 36 for determining the slopes Kin and 2β.

in Figure 3a, which is consistent with eq 38. The downward deviation at high NaOH concentration could be attributed to the ideal gas approximation of eq 37. The slope 2β in the late stage in Figure 2b was plotted as a function of NaOH concentration in Figure 3b. Taking consideration of the experimental error, no significant dependence of 2β on NaOH concentration was observed, which is also consistent with the theory (See eq 36). Figure 4 shows the time development of the gel layer at various acetic acid concentrations in the inner chitosan solution. The behaviors in the initial stage and the late stage were expressed well by linear equations according to eqs 32 and 36, respectively. The slope Kin in the initial stage decreases with acetic concentrations, as shown in Figure 4a. The reciprocal of Kin increases linearly proportional to acetic acid concentration, except for the highest one, as shown in Figure 5a, which is consistent with eq 38. The slight upward deviation at the highest concentration of acetic acid could be attributed to the ideal gas approximation of eq 23. The slope 2β in the late stage in Figure 4b was plotted as a function of acetic acid concentration in Figure 5b. The value of 2β is roughly constant at low acetic acid concentration, whereas 2β slightly deceases with it. This result is consistent with eq 36 derived under the ideal gas approximation. Figure 6 shows the time development of the gel layer at various chitosan concentrations. The behaviors in the initial stage (a) and in the late stage (b) were again expressed well by linear equations


Figure 5. The parameter Kin (a) and 2β (b) as a function of acetic acid concentration Cin.

according to eqs 32 and 36, respectively. The whole behavior of the time development for different chitosan concentrations is almost superposed in the plot of Figure 6. The concentration dependence of upward deviations at the late stage in Figure 6a, however, suggests some effects of chitosan concentration on the dynamics, which was not taken into consideration in the theory. It could be attributed to a small concentration dependence of the diffusion constant of NaOH. Furthermore, if the chitosan solution is very dilute, the gelation should be promoted more easily at high chitosan concentration. Therefore, the independence of time development of the gel layer on chitosan solution should be taken in a limited concentration range. 5. Conclusion


Figure 6. The time course of the gel thickness for different concentrations of chitosan at 0.5 wt % (O), 1 wt % (0), and 2 wt % (∆) in the plot of reduced variables y˜ (a) and x˜ -1/2x˜2 (b) versus ˜t.

where

z˜(x˜ ;h) ≡

∫0

1 1 - x˜ dx˜ 1 - h ln(1 - x˜)

(1 - x˜)ln x˜

(2) The initial stage (in the small ˜t region) is expressed as

( )

z˜ x˜ ;

2β 1 1 1 = y˜ ≡ (1 - x˜)2 ln(1 - x˜) - x˜2 + x˜ ) Kin˜t Kin 2 4 2

where

For a simple case where the gelation occurs by a change of thermodynamic condition but no cross-linking agents are introduced, the equation expressing the dynamics of dialysisinduced gelation was theoretically derived. For the asymptotic behavior in the initial stage and the late stage, some relationships between the parameters in the equation and the concentration of each component given by the experimental condition were derived: (1) The gel layer thickness x and time t are scaled as x/R ) x˜ and t/R2 ) ˜t, and the time development of the gel thickness is expressed independent of the radius R as

( )

z˜ x˜ ;

2β ) Kin˜t Kin

Kin )

γFs RCin

(R and γ are positive constants)

That is, Kin is proportional to NaOH concentration in the extradialytic solution and proportional to the reciprocal of initial acetic acid concentration in the core solution (the intradialytic solution). (3) The late stage (in the large ˜t region) is expressed as

1 x˜ - x˜2 ) 2βt˜ + b 2

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Yamamoto et al.

where the slope 2β does not depend on the initial concentration of acetic acid, Cin. (4) The dynamics in the whole process does not depend on chitosan concentration in a limited range. Using the system chitosan in acetic acid aqueous solution with immersing NaOH aqueous solution, the theoretical prediction was examined. The experimental results were wellexplained by the theory, except for high concentrations of NaOH and acetic acid, where the ideal gas approximation assumed in the theory does not hold. Reasonable agreements of the experimental behavior and the theoretical prediction support the picture for the theory. The simple proportional relation between the concentration of hydroxide anions required to make crosslinkings (FG) and the acetic acid concentration (C) in the sol core, FG ) RC (only one parameter R is required to describe the gelation condition), allows the agreement of the theory and the experimental result. For the DNA gel formation process, such a simple relation could not be expected, and many parameters might be introduced to describe the gelation condition. To identify the gelation condition, the relationship between the thermodynamic condition of the core solution and the conformation and/or the degree of the ionization of polymer molecules should be clarified.

From the above equation, we can rewrite eq A4 as

Here, we show the derivation of eq 26 from eqs 4 and 22. Regarding C as a function of x, we have

dC dC dx ) dt dx dt

dC dC ) K dt dx

1 R (R - x)ln R-x

1 dC 2Rβ 1 )2 dx ˜ A 1 - x˜ C

(A7)

Integrating both sides of the above equation from x˜ ) 0 to x˜ ) x˜, we have finally

Cin

C(x˜) ) 1-2

(A8)

Rβ C ln(1 - x˜) A in

where Cin ) C(x˜ ) 0) ) C(t ) 0). Using the expression K ) A/(RC), we rewrite eq 10, which is equivalent to eq 4, as

dx˜ 1 A ) ˜ RC dt (1 - x˜)ln

(A9)

1 1 - x˜

Substitution of eq A8 into eq A9 gives

[

]

dx˜ 2β ln(1 - x˜) ) Kin 1 Kin dt˜

(A1)

Inserting eq 4 into the above, we have

(A6)

Then,

Acknowledgment. This work was partly supported by Grantin-Aid for Science Research from JSPS (#19540426, #16540366, and #20656129). Appendix

dC 2Rβ C2 )dx A R-x

1 (1 - x˜)ln

1 1 - x˜

(A10) where

Kin )

(A2)

A A ) RCin FG(t ) 0)

(A11)

Solving the differential equation, we have From eqs 22 and A2, we obtain

dC K dx

kAc{gAc(Cs′) - gAc(C0′)} )2 R R (R - x)ln (R - x)2 ln R-x R-x (A3)

( )

z˜ x˜ ;

1

Therefore, the equation for “x-development” of C is given by

2kAc{gAc(Cs′) - gAc(C0′)} 1 dC ) dx K R-x

(A4)

Combining eqs 3 and 5 with the ideal gas approximation (eq 23), we have

kAc{gAc(Cs′) - gac(C0′)} RC Rβ ) - βC ) - C2 K A A

(A5)

2β ) Kin˜t Kin

(A12)

where

z˜ ) z˜(x˜ ;h) ≡

1 1 x˜ x˜ dx˜ 0 1 - h ln(1 - x ˜)

∫

(1 - x˜)ln

(A13)

References and Notes (1) Dobashi, T.; Nobe, M.; Yoshihara, H.; Yamamoto, T.; Konno, A. Langmuir 2004, 20, 6530–6534. (2) Dobashi, T.; Furusawa, K.; Kita, E.; Minamisawa, Y.; Yamamoto, T. Langmuir 2007, 23, 1303–1306. (3) Maki, Y.; Wakamatsu, M.; Ito, K.; Furusawa, K.; Yamamoto, T.; Dobashi, T. J. Biorheol. 2009, 23, 24–28. (4) Narita, T.; Tokita, M. Langmuir 2006, 22, 349–352. (5) Yang, W.; Furukawa, H.; Gong, J. P. AdV. Mater. 2008, 20, 4499– 4503. (6) Furusawa, K.; Minamisawa, Y.; Dobashi, T.; Yamamoto, T. Soft Mater. 2009, 7, 132–149.

Formation of Anisotropic Chitosan Hydrogel (7) Sato, M.; Nobe, M.; Dobashi, T.; Yamamoto, T.; Konno, A. Colloid Polym. Sci. 2005, 284, 293–300. (8) Nobe, M.; Dobashi, T.; Yamamoto, T. Langmuir 2005, 21, 8155– 8160. (9) Lin, S. C.; Minamisawa, Y.; Furusawa, K.; Maki, Y.; Takeno, H.; Yamamoto, T. Colloid Polym. Sci. 2010, 288, 695–701. (10) Furusawa, K.; Minamisawa, Y.; Dobashi, T.; Yamamoto, T. J. Phys. Chem. B 2007, 111, 14423–14430. (11) Chen, R. H. Trans. MRS-J. 2008, 33, 417–424. (12) Druly, J. L.; Mooney, D. J. Biomaterials 2003, 24, 4337–4351.

J. Phys. Chem. B, Vol. 114, No. 31, 2010 10009 (13) Ladet, S.; David, L.; Domard, A. Nature 2008, 452, 76–80. (14) Peppas, N. A.; Hilt, J. Z.; Khademhosseini, A.; Langer, R. AdV. Mater. 2006, 18, 1345–1360. (15) Pilnik, W.; Romboults, F. M. Carbohydr. Res. 1985, 142, 93–105. (16) Sakaguchi, H.; Serizawa, T.; Akashi, M. Chem. Lett. 2003, 32 (2), 174–175. (17) Berger, J.; Reist, M.; Mayer, N. M.; Felt, O.; Peppas, N. A.; Gurny, R. Eur. J. Pharm. Biopharm. 2004, 57, 19–34.

JP102207W

Dynamics in the Process of Formation of Anisotropic Chitosan

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