(SHIKIZAI), 71(1) - J-Stage

3 downloads 0 Views 1024KB Size Report
incorporated by the cyclodextrin, was noticeably larger for the fl-CyD-loaded vesicles than that ..... which is a straight-chain aromatic compound, was determined ...
16

Original Paper J. Jpn. Soc. ColourMater. (SHIKIZAI), 71(1),16-23(1998) Solubilization

of

Aromatic with

Compounds

by

Vesicles

Loaded

Cyclodextrin

Chihiro KAISE*'4,Hideki SAKAI*'**, Yukishige KONDO* *'***, Norio YOSHINO* *'** *, Jiradej Manosroi****, Aranya Manosroi****, Yoshihiro SAITO*** * * and Masahiko ABE*'** Abstract The objective of this study is to raise the solubilizing ability of vesicles consisting of didodecyldimethylammonium bromide (DDAB), a double chain cationic surfactant. We investigated the effects of fl-cyclodextrin (/3-CyD, a water-soluble oligosaccharide capable of incorporating molecules of proper sizes) added to the inner aqueous phase of the vesicles on the solubilization of aromatic compounds with the equilibrium dialysis, fluorescent probe, and dynamic light scattering methods. The size of DDAB vesicles loaded with fi-CyD was found to be 60 nm when they were prepared under ultrasonic irradiation for a sufficiently long time. The solubilization equilibrium constant (K) of benzilic acid, which is a solubilizate hardly incorporated by the cyclodextrin, was noticeably larger for the fl-CyD-loaded vesicles than that for DDAB vesicles containing no cyclodextrin (60 nm), whereas no remarkable increase was found in the K value of 3-phenylpropionic acid (HCA), which is a solubilizate easily incorporated by the cyclodextrin. Consequently, it was concluded that oily substances which are hardly incorporated by fi-CyD are solubilized easily in the vesicle bilayers through the change in the bilayer property caused by the cyclodextrin in the inner aqueous phase of the vesicles. Key- words : Vesicle, cationic surfactant, cyclodextrin, aromatic compounds, solubilization equilibrium constant

Received Jul. 17, 1997 * Faculty of Science and Technology, Science University of Tokyo (2641, Yamazaki, Noda, Chiba 278) ** Institute of Colloid and Interface Science, Science University of Tokyo (1-3, Kagurazaka, Shinjuku-ku, Tokyo 162) *** Faculty of Engineering, Science University of Tokyo (1-3, Kagurazaka, Shinjuku-ku, Tokyo 162) **** Faculty of Pharmacy, Chiang Mai University.(Chiangmai 50200, Thailand) ***** College of Pharmacy , Nihon University(7-1, Narashinodai, 7-Chome, Funabashi, Chiba 274) 4 Present Address Shu Uemura Cosmetics Inc. (4-23-5 Sakuragaoka, Setagaya, Tokyo 156)

1. Surfactant

Introduction

molecules

form colloidal

aggre-

gates of various shapes and sizes, such as spherical micelle, rodlike micelle, hexagonal liquid crystal, lamellar liquid crystal, etc., in aqueous solution, according to the balance between the area occupied by their hydrophilic part and the volume occupied by their hydro16

JJSCM, 71 (1) (1998

Solubilization

of Aromatic

Compounds

Loaded

with Cyclodextrin

17

(aromatic compounds) would increase. In this study, we adopted fl-cyclodextrin (j3-CyD),

phobic part. Vesicles are also a form of colloidal aggregates of surfactant molecules and have a bimolecular membrane structure that encloses an aqueous phase.1'2)

which is hydrophilic, cylindrical in shape, and capable of including other molecules of proper size inside, as the incorporating agent, and 3-

In recent years, vesicles have attracted attention as a model of biological membranes and a carrier

by Vesicles

phenylpropionic acid and benzilic acid as the solubilizates: The former is easily included and

of drugs in drug delivery systems

(DDS). Attention has also been given to vesicles because they have been applied in the field of organic chemical reactions in industry, a

the latter hardy included in P-CyD. Then, vesicles loaded with aqueous g-CyD solution were prepared, each of the two solubilizates

collector of organic substances in higher order filtration, and a sensor-base material for stimulus - responsive membranes.3-5) Dissolution

g-CyD was examined on the solubilization equilibrium constants of the solubilizate.

was solubilized in the vesicles, and the effect of

or solubilization of hydrophobic substances like aromatic compounds becomes essential in the bilayers

2.

Experimental

2.1 Materials

of vesicles in these applications.

We have reported solubilization of aromatic compounds with a polar group with vesicles of different sizes prepared using double chain

2.1.1 Surfactant Reagent grade mounium bromide

cationic surfactants of different alkyl chain lengths (dialkyldimethylammounium bromides) in our earlier paper.6'7) The all of the

Kogyo), was used as supplied as the vesiclef orming surfactant. 2.1.2 Water - soluble (incorporating) sub-

aromatic

stance The incorporating

compounds

used were found to be

solubilized in the vesicle bilayers, that is, in the hydrophobic region. It was also revealed that

didodecyldimethylam(DDAB, Tokyo Kasei

agent, /3-CyD, a reagent

grade (Tokyo Kasei Kogyo), was used without further purification. Scheme 1 shows its chemical structure.

the solubilization equilibrium constant is independent of vesicle size for the compounds having a polar group that is hardly dissociable in water, for example, 2-phenylethanol, whereas the constant increases considerably with increasing vesicle size for the compounds having a polar group that is dissociable in water, for instance, benzoic acid and 3-phenylpropionic acid. These results suggest that an increase in vesicle size brings about an increase in the solubilization equilibrium constant

for aromatic

compounds

Scheme

1

Structure

of j3-cyclodextrin.

2.1.3 Solubilizates The aromatic solubilizates employed were 3 -phenylpropionic acid (HCA , hydrocinnamic

with a polar

group that dissociates in water. One of the characteristics of vesicles is their ability to retain water-soluble substances in

acid), which is easily included by /3-CyD, and benzilic acid, which is hardly included by /3CyD. Their chemical structures are shown in Scheme 2.

the internal aqueous phase.' If water-soluble substances can be incorporated into the internal aqueous phase of vesicles, the total solubilized (incorporated) amount of these substances 17

18

Original

Paper

SHIKIZAI

solubilization vesicle

equilibrium

and bulk phase,

aromatic

compounds

constant

between

K, was defined by

the

for the

following

equa-

tion,

(1) where Xvesicie is given by the ratio, (concentraScheme

2

Structures

of aromatic

2.1.4 Fluorescence probe As a fluorescent probe,

tion of aromatic compound solubilized by vesicles)/ {(concentration of vesicle-forming surfactant) + (concentration of aromatic com-

compounds.

ammonium

8-

pound solubilized by vesicles)} , and Xbuik is the mole fraction of aromatic compound remaining in the bulk phase. Equation 1 indicates that the larger the value of K is, the

anilinonaphthalene-l-sulfonate (ANS, Wako Pure Chemical), was used after recrystallization from ethanol. 2.1.5 Water Distilled water for injection according to the

greater the amount partitioned (solubilized) of aromatic compound in vesicles is. Determination of solubilization equilibrium

Pharmacopoeia of Japan (Ohtsuka Pharmaceutical Co.) was used as supplied (pH 6.3). 2.2 Methods 2.2.1 Preparation CyD solution

constant dialysis

was performed by the equilibrium (ED) method as in the previous

of vesicles loaded with /3-

papers.6'7'9) Solubilized solution was placed in the compartment on the retentate side of an

Preparation of /3-CyD-loaded vesicles was done by the ultrasonic irradiation method." An aqueous solution of DDAB (10mM) contain-

equilibrium dialysis cell with a cellulose acetate membrane of MWCO (molecular weight cutoff) 6000 and water in the compartment on

ing 1mM of /3-CyD was irradiated in an ultrasonic irradiator (Branson Cleaning Equipment, Type B-220; output power 125 W) at a temper-

the permeate side of the cell. After the cell was left standing at 30°C for over 40 h, the concentrations of surfactant and aromatic compound were measured and K was calculated using by

ature higher than Tc of DDAB (10°C) for 120 min or more to yield a vesicle dispersion. The dispersion membrane molecular

was then dialyzed using a cellulose impermeable to substances of weights higher than 13000 Da to

(2)

remove /3-CyD remaining in the bulk phase. 2.2.2 Preparation of solubilized systems

where [0], [S], and Cu,are the molar concentrations of aromatic compound, surfactant, and water (55.4mol/dm3), respectively, and ret and per denote the solutions on the retentate and permeate sides, respectively. Here, [S] Per and [0] per are equal to the concentrations of surfactant monomer and aromatic compound remaining unsolublized in the bulk phase respectively, and {[S] ret [S] ber} and { [0] „t- [01per} represent the concentrations

Vesicle-solubilized solutions were prepared in the following way. A given amount of each of the aromatic compounds was added to /3CyD-loaded DDAB vesicle solutions previously incubated for over 12 h at 30°C and the mixtures were stirred for a long time (3 h). The solubilized systems were left at 30°C for over 36 h to attain a solubilization equilibrium. 2.2.3 Determination rium constant According

to

of solubilization

equilib-

of surfactant

our

earlier

papers'''),

the

compound 18

forming solubilized

vesicles in vesicle,

and

aromatic

respectively.

JJSCM,

71 (1) (1998)

Solubilization

of Aromatic

Compounds

by

The Orange II method') was also used to determine the surfactant monomer concentration in the permeate side solution ([S] Per)after equilibrium dialysis experiment. The concentration was found to be less than 0.07 mmol/ dm3 and hence the concentration of surfactant forming vesicles, {[S] ret—LS1 per}, was approximated by the total surfactant concentration (0.010 mol/dm3). The value of K was then calculated by equation 3 since

Vesicles

cence

Loaded

with

Cyclodextrin

polarization

P,

19

was

calculated

using

equation

The measurement

(4) was done at 30°C using an

exciting wavelength of 380 nm and a fluorescence detecting wavelength of 465 nm. 2.2.6 Measurement of potential The vesicle-forming

surfactant

used in the

present work is a cationic one and hence the surface of vesicles before and after solubilizing aromatic compound is positively charged. The potential of vesicles was measured by

(3) of the concentration of

the fringe mode laser Doppler electrophoresis method using a potential measuring appara-

aromatic compound was performed with a double beam spectrophotometer (Shimadzu Model MPS-2000) at its maximum absorption

tus (Malvern Zetasizer IL). The light source was He-Ne laser (Coherent; maximum power

The determination

wavelength. 2.2.4 Particle

output 15 mW, wavelength 632.8 nm) and all measurements were made at 30°C.

size measurement

3.

The vesicle size was measured by the dynamic light scattering method9) using a Submicron Particle Analyzer (Malvern System

Results

3.1 Stability

and Discussion

of /3-CyD-loaded

vesicles

DDAB vesicles were used in this study, which are known to have a good stability over

4700) equipped with an argon ion laser (Coher-

a long storage time.6'7 While various concentrations of aqueous /3-CyD solution were en-

ent Innova 90, maximum output power 5000 mW) at an angle of 90° and at 30°C. 2.2.5 Preparation of vesicles containing

ANS was

closed in their inner aqueous phase, the vesicles were sufficiently exposed to ultrasonic irradiation for the minimizing of their size. The long-term stability of /3-CyD-loaded

conducted as follows. An aliquot of ethanolic ANS solution was taken in a test tube with

vesicles was first examined by leaving them to stand at 30°C. When the concentration of g-

screw cap and the solvent was removed under reduced pressure to leave a thin film of ANS

CyD was higher than 10 mM, deposition of the surfactant was observed soon after vesicles

on the test tube wall. An aqueous solution containing vesicles of the double chain cationic surfactant (10 mmol/dm3) was added to this

formed.

test tube to be the ANS concentration 0.5 x 10-3 mmol/dm3 and then the solution was left standing for 24 h. In this way, a fluorescent

vesicle preparation. Since no surfactant deposition was observed at j3-CyD concentrations below 1 mM, this concentration was used

probe-loaded vesicle solution was obtained. A fluorophotometer (Shimadzu Model RF-

hereafter for fl-CyD in this study. 3.2 Solubilization equilibrium constant

3000) was used to measure the intensities of vertical and parallel polarizations (I i and I §)

The effect of g-CyD in the inner phase of vesicles was examined on the solubilization

to the exciting

equilibrium

fluorescent probe and measurement escence polarization Preparation of vesicles containing

of fluor-

No stable vesicles were obtained

/3-CyD concentrations surfactant deposition

light, and the degree of fluores19

constant

at

of 2-5 mM because of occurred 3 days after

of aromatic

compounds.

20

Fig. 1

Original

Solubilization constants of HCA vesicle containing /3-cyclodextrin.

Paper

in DDAB Fig. 2

Vesicles of double-chain cationic surfactant molecules become more stable against aggre-

Solubilization DDAB vesicle

constants containing

of benzilic acid /3-cyclodextrin.

in

of vesicles in the figure. The K value for HCA decreased with increasing X in all cases. Namely, the solubil-

gation and fusion as the vesicle size decrease.6,10,11) Hence, the /3 - CyD - loaded

izing ability of vesicles for HCA decreased as the concentration of the solubilizate increased

vesicles used in the present study were exposed to ultrasonic irradiation for a sufficiently long time to minimize the vesicle size. This treatment brought about a size of 60 nm for /3-CyD -loaded DDAB vesicles , which was larger than that (20 nm) for the vesicles containing no /3-

in vesicles. It was also found that the K value for DDAB vesicles containing fl-CyD (60 nm) was larger than that for the vesicles without /3 -CyD (20 nm) . This is understandable from view of the finding in the earlier papers6'7) that the K value increases with increase in vesicle

CyD, due probably to the fact that the presence of /3-CyD in the inner aqueous phase increased

size. CyD

its volume, and consequently, the vesicle size. This trend is in accordance with that observed

The K value for the vesicles with /3(60 nm) was found to be slightly higher

than that for without /3-CyD (60 nm). This is due presumably to incorporation of HCA by p -CyD . The solubilization equilibrium con-

for vesicles loaded with aqueous glucose solution.12) Because /3-CyD is said to easily incorporate

stant is thought to increase through incorporation and concentration of straight-chain aromatic compounds like HCA by fi-CyD in the

straight chain aromatic compounds, the solubilization equilibrium constant, K, of HCA, which is a straight-chain aromatic compound,

inner aqueous phase of vesicles. The relation between K and

was determined for DDAB vesicles loaded with /3-CyD and those without fl-CyD (Fig. 1). The data for DDAB vesicles without

SHIKIZAI

examined compound

/3-CyD

X

was

using benzilic acid, an aromatic hardly incorporated by /3-CyD, as

the solubilizate (Fig.2). The K value for fl-CyD-loaded DDAB vesicles was found considerably to be larger than

(60 nm) are also shown in the figure for comparison. The solubilization equilibrium constant, K, is plotted against the mole fraction, X, of solubilizate (aromatic compound) inside

that for the vesicles without fl-CyD. The effect of the cyclodextrin was more remark20

JJSCM, Table

1

71(1)

(1998)

Zeta-potential

Solubilization

of the vesicle

of Aromatic

surface

Compounds

at 30°C

by Vesicles

Loaded

with Cyclodextrin

21

When the K values for DDAB vesicles without /3-CyD in the HCA and benzilic acid solubilizing systems were compared, the value was found higher in the latter system than in the former system. HCA and benzilic acid are aromatic

able in this case than the case involving straight chain aromatic compound Benzilic acid has a branched structure,

in which

with a hydrophilic

group dissociable in water and solubilized in the vicinity of the bilayer surface of DDAB vesicles. The pKa for HCA and benzilic acid

the

(Fig. 1). molecular

two hydrophilic

compounds

are 4.66 and 3.04'4), respectively. The fact that the K value of benzilic acid is larger than

groups.

that of HCA would be interpreted, therefore, as showing that benzilic acid dissociates more

(-OH and -COOH) are attached to the carbon atom that connects two aromatic rings, and hence, is hardly incorporated by g-CyD.13)

easily in water and combines more strongly with the hydrophilic groups on the vesicle

Those aromatic compounds, which branched molecular structure and

have a possess

surface, thereby being solubilized more readily than HCA.

hydrophilic groups, are expected to be solubilized by adsorbing to the hydrophilic groups on

3.3 Microscopic viscosity of vesicle bilayers Since aromatic compounds with hydrophilic

the surface of vesicle bilayers. In view of this, the potential was measured of /3-CyDloaded DDAB vesicles with solubilized benzilic

groups are solubilized in the hydrophobic region adjacent to the hydrophilic moiety of vesicles,"-") changes in the state of vesicle bilayers were supposed to appreciably affect

acid and DDAB vesicles (60 nm) to check the adsorbed state of the solubilizate on the outer

the K value in both the HCA and benzilic acid solubilizing systems. The degree of ANS fluorescence polarization was measured on

vesicle surface (Table 1). As is seen in the table, the potential of g -CyD-loaded DDAB vesicles with solubilized

HCA or benzilic acid solubilizing and ANS containing DDAB vesicles (20 nm) and g-CyD -loaded DDAB vesicles (60 nm) for the exami-

benzilic acid is about 40 mV, which is appreciably lower than 80 mV for DDAB vesicles. This suggests that dissociated benzilic acid anions adsorb on the outer surface of /3-CyDloaded DDAB vesicles to reduce the surface

nation of the state of the hydrophilic moiety of

potential of the vesicles. The increased K value for /3-CyD-loaded DDAB vesicles would

polarization, P, and the concentration of aromatic compound, X, for HCA and benzilic acid, respectively. The P value was lower for the bilayers of g -CyD-loaded DDAB vesicles than for those of

the vesicles. tion between

be caused by a high adsorbability of benzilic acid to the hydrophilic outer bilayer surface of the vesicles.

DDAB vesicles containing

The experimental findings mentioned so far imply that changes in the properties of vesicle bilayers

(e. g. reduction

in bilayer

Figures 3 and 4 show the relathe degree of ANS fluorescence

no cyclodextrin

both the HCA and benzilic systems.

viscosity)

In general,

produced by /3-CyD addition may be responsible for the increase in K value when the solubilizate is hardly incorporated by the cyclodextrin.

polarization

the degree of ANS fluorescence increases

with

increase

in the

packing density of the hydrophilic groups surfactant molecules in the vesicle surface. 21

in

acid solubilizing

of In

22

Fig. 3

Original

SHIKIZAI

Paper

Fig. 4 Relationship between the degree of ANS fluorescence polarization (P) in DDAB vesicles containing /3-cyclodextrin and the concentration of Benzilic acid.

Relationship between the degree of ANS fluor escence polarization (P) in DDAB vesicle containing /3-cyclodextrin and the concen tration of HCA.

order for the packing density of the surface hydrophilic groups (cationic groups in our

bilayers

on both inner aqueous and outer bulk

case) to become higher, it is said to be essential that the electrostatic repulsion between the

phases. From what we have mentioned so far, we would be able to give the following explana-

hydrophilic adsorption

tions to the finding that the P value for /3-CyD -loaded DDAB vesicles was lower than that

groups involved is reduced by the of the oppositely charged species

(anions in our case) to the surface hydrophilic

for DDAB vesicles containing

groups and the hydrophilic groups involved are dehydrated."") Also, we reported in our previous paper6'7) that the change in P value obser-

in the presence of either HCA or benzilic acid. An increase in vesicle size causes a lowering in the microscopic viscosity of vesicle surface as reported in the earlier paper,7) suggesting the

ved when oily substances are solubilized in the vesicle bilayers becomes smaller as the vesicle size is reduced because the hydration structure

presence of /3-CyD molecules on the vesicle bilayer surface on the inner aqueous phase side. It is possible then that this microscopic

is more rigid for smaller vesicles. Hence, the small changes in P value in the figures caused

viscosity in the presence of /3-CyD was also measured simultaneously in the measurement of the degree of ANS fluorescence polariza-

by incorporation of aromatic compounds in /3 -CyD-loaded DDAB vesicles would be due to the possible presence

of rigid hydration

struc-

tion. The P values in Figs. 3 and 4 are probably those for the vesicle bilayers but not give

ture in these vesicles as in small vesicles. The finding that the P value started rising at a lower solubilizate concentration in the benzilic

the microscopic viscosity of /3-CyD solution (1 mM) because the P value for /3-CyD solution

acid solubilizing system than in the HCA solubilizing system for fl-CyD-loaded DDAB

(1 mM) containing 4.

vesicles would be interpreted by the fact that benzilic acid molecules are bound to the hydro-

ANS was 0.07. Conclusions

The size of DDAB vesicles was found to increase when /3-CyD, which is a water-soluble substance capable of incorporating mole-

philic groups of DDAB on the vesicle bilayer surface more strongly than HCA molecules. ANS can also be present in the vesicle

cules of suitable sizes, was dissolved in their inner aqueous phase. No appreciable increase was obtained in the solubilization equilibrium

bilayer surface on the inner aqueous phase side,'548) and hence, the degree of ANS fluorescence polarization is dependent on the packing density of the hydrophilic

no cyclodextrin

constant

groups in the vesicle

pound 22

of HCA, which is an aromatic easily

incorporated

by /3-CyD,

comwith

JJSCM,

71(1)

addition

Solubilization

(1998)

of the cyclodextrin

ous phase an aromatic

constant compound

the cyclodextrin, the cyclodextrin microscopic

viscosity

caused

acid, which if

in the inner aque-

to a reduction of the

by

increased

vesicle

in the bilayer

by the oligosaccharide. References

1) Y. Kondo, 2) 3)

4) 5)

6)

N. Yoshino

: Hyomen,

350,

Vesicles

Loaded

with

23

Cyclodextrin

7) C. Kaise, H. Sakai, Y. Kondo, N. Yoshino, M. Abe : J. Jpn. Soc. Colour Mat., 70, 242 (1997). 8) S. Tsuji : "Technology of Solubilization and Emulsification", Kogaku-Tosho, p. 115 (1992). 9) H. Uchiyama, S. D. Christian, J. F. Scamehorn, M. Abe, K. Ogino, : Langmuir, 7, 95 (1991). 10) K. Deguchi, J. Mino : J. Colloid Interface Sci., 65, 1 (1978). 11) L. A. M. Rupert, D. Hoekstra, J. B. F. N. Engberts : J. Am. Chem. Soc., 107, 2628 (1985). 12) Y. Kondo,M. Abe, K. Ogino, H. Uchiyama, E. E. Tucker, J. F. Scamehorn, S. D. Christian : Colloid Surf., B: Biointerfaces, 51, 1 (1993). 13) Y. Shiraishi, H. Hirai : Hyomen, 293, 34 (1996). 14) Chem. Soc. Jpn., "Kagakubinnrann. Kisohen", 11-320 and 321, Maruzen (1993). 15) B-H. Lee, S. D. Christian, E. E. Tucker, J. F. Scamehorn : Langmuir, 6, 230 (1990). 16) M. Abe, K. Mizuguchi, Y. Kondo, K. Ogino, H. Uchiyama, J. F. Scamehorn, E. E. Tucker, S. D. Christian : J. Colloid Interface Sci., 160, 16 (1993). 17) Y. Kondo, K. Mizuguchi, Y. Tokuoka, H. Uchiyama, K. Kamogawa, M. Abe . J. Jpn. Soc. Colour Mat., 68, 271 ( 1995 ). 18) T. Inoue, Y. Muraoka, K. Fukushima, R. Shimozawa : Chem. Phys. Lipids, 46, 107 (1988).

hand,

incorporated

was considerably

by

aque-

other

of benzilic

was present

due presumably

surface

On the

hardly

ous phase

Compounds

to the inner

of the vesicles.

the equilibrium

of Aromatic

34

(1996). A. D. Bangham, M. M. Standish, J. C. Watkins : J. Mol. Biol., 13, 238 (1965). J. Sunamoto, K. Akiyoshi, "Liposomes", S. Nojima, J. Sunamoto, K. Inoue, Eds. Nankoudo, p. 283 (1988). M. Abe, Y. Kondo : Mater. Technol., 10, 275 (1992). Y. Kondo, M. Abe, K. Ogino, H. Uchiyama, J. F. Scamehorn, E. E. Tucker, S. D. Christian : Langmuir, 9, 899 (1993). Y. Kondo, N. Yoshino, C. Kaise, H. Sakai, M. Abe : J. Jpn. Oil Chem. Soc., 46, 323 (1997).

シ ク ロ デ キ ス ト リ ン を 内 包 した べ シ ク ル に よ る 芳 香 族 化 合 物 の 可 溶 化

貝 瀬 千 尋*・ 酒 井 秀 樹*'**・ 近 藤 行 成*好 野 則 夫**'***・ ジ ラ デ ィ ・マ ノ ス ロ イ****,ア ラ ー ニ ャ ・マ ノ ス ロ イ****, 斎 藤 好 廣*****,阿

部 正 彦*'**

*東 京 理 科 大 学 理工 学部 工 業 化学 科 〒278千 葉 県 野 田市 山崎2641 **東 京 理 科 大 学 界面 科学 研 究所 〒162東 京 都 新 宿 区 神 楽 坂1-3 ***東 京 理 科 大 学工 学 部工 業化 学 科 〒162東 京 都 新 宿 区 神 楽 坂1-3 ****チ ェ ンマ イ大 学 薬 学 科 タ イ 国 チ ェ ンマ イ市 *****日 本 大 学薬 学部 〒274千 葉 県 船 橋 市 習 志 野 台7-7-1

要 二 鎖 型 カ チオ ン界 面 活 性 剤(ジ



ドデ シ ル ジメ チ ル ア ンモ ニ ウ ム プ ロ ミ ド;DDAB)ベ

シク ル の 可 溶 化 能 を 向

上 させ る要 因 を 検 討 す るた あ,ベ シ クル の 内 水 相 に シ ク ロ デ キ ス トリ ン(β 一CyD;水 溶 性 物 質 で あ り,か っ, 適 当 な大 きさ の分 子 を包 接 可 能 な物 資)を 内包 させ,そ の 芳 香 族 化 合 物 の 可 溶 化 に 及 ぼ す 影響 に つ い て,平 衡 透 析 法,蛍 光 プ ロー ブ法,動 的光 散 乱 法 に よ り検 討 した。 そ の結 果,超 音 波 を十 分 照 射 して調 製 した β一CyD内 包DDABベ

シ ク ル の粒 子 径 は60nmに

な っ た。 ま た,

芳 香 族 化 合 物 と して β→CyDに 包 接 され に くい ベ ン ジル 酸 を 用 い た 場 合 に は,β 一CyD内 包DDABベ シ クル の 可 溶 化 平 衡 定 数(K)の 値 は 粒 子 径 が60nmのDDABベ シ ク ル に比 べ 顕 著 に増 加 した が,β 一CyDに 包 接 され るHCAを 用 いた 場 合 に はK値 の 大 き な増 加 は確 認 され な か っ た。 したが って,β →CyDに 包 接 さ れ に くい油 性 物 資 は,内 水 相 に β一CyDが 存 在 す る こ とに よ り生 じる ベ シク ルニ 分 子 膜 の 物 性 変 化 に よ り,可 溶 化 され や す くな る ことが 明 らか と な っ た。 23