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
旨
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
