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18
Chemistry Letters Vol.37, No.1 (2008)
Specific Fixed Aqueous Layer of Three-component Hybrid Liposomes Related to
Inhibition of Hepatoma Cells Growth
ꢀ
Yoko Matsumoto, Yoshihiro Tanaka, Koichi Goto, and Ryuichi Ueoka
Graduate Course of Applied Life Science, Sojo University, 4-22-1 Ikeda, Kumamoto 860-0082
(Received October 12, 2007; CL-071125; E-mail: matumoto@life.sojo-u.ac.jp)
It is noteworthy that the thickness of fixed aqueous layer
TFAL) of three-component hybrid liposomes (THL) composed
CH2OAc
CH2OAc
AcO
H
O
H
O
OAc
H
(
H
H
H
O
OAc
H
OAc
of L-ꢀ-dimyristoylphosphatidylcholine (DMPC), polyoxyethyl-
ene (20) sorbitan monolaurate (Tween 20), and decyl-ꢁ-lacto-
pranoside (LactC10) (DMPC:Tween 20:LactC10 = 65:7:28)
was about twice that of two-component hybrid liposomes (HL)
composed of DMPC and Tween 20. It is also attractive that
THL could remarkably inhibit the growth of hepatoma cells.
H
H
OAc
H
OAc
1
CH OAc
CH OAc
2
2
CH (CH ) OH/BF Et O AcO
·
O
H
H
O
O(CH ) CH
2 9
3
2
n
3
2
3
H
H
abs. CH Cl
O
O
2
2
OAc
H
OAc
H
H
H
H
H
0.88g 25% yield
H
OAc
H
OAc
2
3
CH OH
2
CH OH
2
Biological membranes provide compartments of defined
sizes, shapes, and microenvironments. They organize living mat-
ter in the cell, create a fluid two-dimensional matrix. There are
wide variations in the types of lipids including phospholipids
and proteins as well as in their ratios. Such variations in lipids
should take an important role for the activation of bioactive sub-
stances. In the course of our study of esterase models, remarka-
bly stereospecific catalysis was observed in the hydrolysis of
amino acid and/or dipeptide esters carried out by functional
molecular assemblies composed of surfactants and catalytic
species.1
OH
H
O
H
O
H
O(CH2)9CH3
H
abs. MeOH/NaOMe
.36g 78% yield
H
H
OH
OH
0
H
OH
H
OH
Scheme 1. Synthesis of 3 (decyl-ꢁ-lactopyranoside: LactC10).
ꢁ
55.45; H, 9.13%. 0.36 g, 78% yield. mp: 185.6–186.5 C. IR
ꢂ1
1
(KBr): ꢂ (cm ) 3424, 2921, 2853, 1064. H NMR (270 MHz
in DMSO-d6): ꢃ 5.10 (1H, s, OH), 5.08 (1H, s, OH), 4.80 (1H,
br s, OH), 4.66 (2H, s, OH ꢃ 2), 4.54 (2H, m, OH ꢃ 2), 4.18
(1H, d, J ¼ 7:91 Hz, CH), 4.15 (1H, d, J ¼ 7:92 Hz, CH), 3.76–
3.27 (13H, m, CH ꢃ 9, CH2 ꢃ 2), 2.98 (1H, m, CH), 1.51 (2H,
m, CH2), 1.25 (14H, br s, CH2 ꢃ 7), 0.85 (3H, t, J ¼ 6:92 Hz,
CH3).
–3
It is well known that saccharides play important roles in ad-
hering to cells, transmitting information, recognizing molecules
4
on the cell membranes thought receptors including lectin. For
5
example, lactose was found in molecular recognition in vivo.
Hydration of saccharides with hydrogen bonds provides stability
to the structure of water. The hydration of sugar derivatives was
Secondly, we examined the thickness of fixed aqueous layer
1
5
(TFAL) of THL from zeta potential (ꢄ). THL was prepared
by sonication of a mixture of DMPC, Tween 20, and 3
(DMPC:Tween 20:3 = 65:7:28) with a sonicator (VS-N300,
6
discussed in relation to the hydration of the parent sugars. Re-
cently, the preparation and characterization of glyco-liposomes
have been reported.7
We have developed HL composed of vesicular and micellar
ꢁ
VELVO-CLEAR) at 45 C under a nitrogen atmosphere with
300 W in phosphate-buffered saline (PBS(ꢂ)) solution contain-
ing various concentrations of NaCl (10, 50, 200, and 400 mM),
followed by filtration with a 0.45-mm filter. ꢄ of the sample solu-
tions were measured by laser doppler photometry method using
an electrophoretic light scattering spectrophotometer (ELS-
8000, Otsuka Electronics) with a He–Ne laser as light source
(633 nm, 10 mW) at the scattering angle of 20 . ꢄ was calculated
from electrophoretic mobility (U: m Volt
eq 1 (smoluchowski equation).
1
,8
molecules have been produced. HL without drugs inhibited the
proliferations of various tumor cells along with apoptosis in vitro
and in vivo.9
–12
In this study, we report that the lactose surfactant was
synthesized by glycosylation and deacetylation, which were al-
lowed to experiment as the relevance to hydration and antitumor
effects of THL composed of L-ꢀ-DMPC, polyoxyethylene (20)
sorbitane monolaurate (Tween 20), and decyl-ꢁ-lactopranoside
ꢁ
2
ꢂ1 ꢂ1
s ) applying the
(
LactC10) on the growth of hepatoma cells in vitro.
ꢄ ¼ 4ꢅꢆU="
ð1Þ
Firstly, we prepared LactC10 (decyl-ꢁ-lactopranoside) from
2
Ac-LactC10 (decyl-ꢁ-lactose heptaacetate), which was obtained
by glycosylation and deacetylation of Ac-Lact (ꢁ-lactose octa-
acetate)1 (Scheme 1). 3 was prepared from 1 by glycosylation
at C-1 site of D-glucose unit with 1-decanol and boron trifluoride
diethyl etherate in dry dichloromethane, followed by deacetyla-
tion of acetyl groups by treatment with sodium methoxide in ab-
solute methanol.
Satisfactory elemental, IR, and H NMR analyses were ob-
tained for 3 and we successfully produced the lactose surfactant.
Anal. Calcd for C22H42O11: C, 55.88; H, 9.13%. Found: C,
where ꢆ (Pa.s) and " (N/Volt ) are the viscosity and permittivity
of solvent, respectively. ꢄ was measured at 37 C. ꢄ is defined as
the electrostatic potentials at the position of the slipping plane ꢀ
(nm), which occurs just outside the fixed aqueous layer of THL.
Then, ꢄ is expressed as eq 2.
ꢁ
3,14
lnðꢄÞ ¼ ln A ꢂ ꢀꢇ
where ꢇ is Debye–H u¨ ckel parameter (=3.3 c; c: M for NaCl). If
the ꢄ is measured in various concentrations of NaCl and plotted
against ꢇ, the slope gives the position of the slipping plane or the
ð2Þ
pffiffiffiffiffiffi
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Copyright ꢀ 2008 The Chemical Society of Japan
Matsumoto, Yoko
