Abstract
The binding of β and γ-cyclodextrins with the anti-cancer drug doxorubicin has been examined with the use of fluorescence and absorbance spectroscopy, circular dichroism measurements, and proton NMR spectroscopy. The stoichiometry of the complexes formed and their apparent formation constants have been estimated with the use of various approaches. The stoichiometrics for both the β-cyclodextrin-doxorubicin complex and the γ-cyclodextrin-doxorubicin complex have been determined to be predominantly 1:1. The strength of the interaction of the drug with γ-cyclodextrin is stronger than that with β-cyclodextrin. The effect of varying the pH on the calculated formation constants of the complexes has also been investigated.
Get full access to this article
View all access options for this article.
References
1.
Sturgeon
R. G.
and
Schulmann
S. G
, J. Pharm. Sci. 66 , 958 (1977 ).
2.
Chaires
J. B.
Dattagupta
N.
and
Crothers
D. M
, Biochemistry 21 , 3933 (1982 ).
3.
Eriksson
M.
Norden
B.
and
Eriksson
S
, Biochemistry 27 , 8144 (1988 ).
4.
Rizzo
V.
Sacchi
N.
and
Menozzi
M
, Biochemistry 28 , 274 (1989 ).
5.
Zunino
F.
Dimarco
A.
Zaccara
A.
and
Gambetta
R. A
, Biochim. Biophys. Acta 607 , 206 (1980 ).
6.
Angeloni
L.
Smulevich
G.
and
Marzocchi
M. P
, Spectrochim. Acta, Part A 38A , 213 (1982 ).
7.
Xodo
L. E.
Manzini
G.
Ruggiero
J.
and
Quadrifoglio
F
, Biopolymers 27 , 1839 (1988 ).
8.
Gabbay
E. J.
Grier
D.
Fingerle
R. E.
Reimer
R.
Levy
R.
Pearce
S. W.
and
Wilson
W. D
, Biochemistry 15 , 2062 (1976 ).
9.
Mondelli
R.
Ragg
E.
Fronza
G.
and
Arnone
A
, J. Chem. Soc., Perkin Trans 2 , 51 (1987 ).
10.
Pachter
J. A.
Huang
C. H.
Duvernay
V. H.
Jr.
Prestayko
P. W.
and
Crooke
S. T
, Biochemistry 21 , 1541 (1982 ).
11.
Olson
H. M.
and
Capen
C. C
, Lab. Investig. 37 , 386 (1977 ).
12.
Rosenoff
S. H.
Olson
H. M.
Young
D. M.
Bostick
F.
and
Young
R. C
, J. Natl. Cancer Inst. 55 , 191 (1975 ).
13.
Karczmar
G. S.
and
Tritton
T. R
, Biochim. Biophys. Acta 557 , 306 (1979 ).
14.
Sawaya
A.
Benoit
J.-P.
and
Benita
S
, J. Pharm. Sci. 76 , 475 (1987 ).
15.
Burke
T. G.
Israel
M.
Seshadri
R.
and
Doroshow
J. H
, Biochim. Biophys. Acta 982 , 123 (1989 ).
16.
Szejtli
J.
, Cyclodextrins and their Inclusion Complexes (Akademiai Kiado , Budapest , 1982 ).
17.
Vikmon
M.
Stadler-Szoke
A.
Hortobagyi
G.
Kolbe
I.
and
Szejtli
J
, Acta Pharm. Technol. 32 , 29 (1986 ).
18.
Nakai
Y.
Yamamoto
K.
Terado
K.
and
Akimoto
Y
, Chem. Pharm. Bull. 23 , 1205 (1975 ).
19.
Tokumura
T.
Nanba
M.
Tsushima
Y.
Tatsuishi
K.
Kayano
M.
Machida
Y.
and
Nagai
T
, J. Pharm. Sci. 75 , 391 (1986 ).
20.
Uekema
K.
Fuginaga
T.
Hirayama
F.
Otigari
M.
Yamasaki
M.
Seo
H.
Hashimoto
T.
and
Tsuruoka
M
, J. Pharm. Sci. 72 , 1338 (1983 ).
21.
Bekers
O.
Beijnen
J. H.
Vis
B. J.
Suenaga
A.
Otagiri
M.
Bult
A.
and
Underberg
W. J. M
, Int. J. Pharm. 72 , 123 (1991 ).
22.
Sanchez
G. F.
Lopez
M. H.
and
Heredia
H
, Anal. Chim. Acta 187 , 147 (1986 ).
23.
Kuboyama
A.
and
Matuzaki
S. Y
, J. Incl. Phenom. 2 , 755 (1984 ).
24.
Sanchez
G. F.
Lopez
M. H.
and
Gomez
J. C. M
, Analyst 112 , 1037 (1987 ).
25.
Lehmann
J.
and
Klienpeter
E
, J. Incl. Phenom. 10 , 233 (1991 ).
26.
Inoue
Y.
Kuan
F.
and
Chujo
R
, Bull. Chem. Soc. Jpn. 60 , 2539 (1987 ).
27.
Suzuki
M.
Sasaki
Z.
Szejtli
J.
and
Fenyvesi
E
, J. Incl. Phenom. 5 , 459 (1987 ).
28.
Inoue
Y.
Takahashi
Y.
and
Chujo
R
, Carbohydr. Res. 148 , 109 (1986 ).
29.
Demarco
P. V.
and
Thakkar
A. L
, Chem. Commun. 2 (1970 ).
30.
Turro
N. J.
Okubo
T.
and
Chung
C. J
, J. Am. Chem. Soc. 113 , 1789 (1982 ).
31.
Muñoz de la Peña
A.
Ndou
T. T.
Zung
J. B.
Greene
K. L.
Live
D. H.
and
Warner
I. M
, J. Am. Chem. Soc. 113 , 1572 (1991 ).
32.
Benesi
A. H.
and
Hildebrand
J. H
, J. Am. Chem. Soc. 71 , 2703 (1949 ).
33.
Kondo
H.
Nakatani
H.
and
Hiromi
K
, J. Biochem. 79 , 393 (1976 ).
34.
Djedaini
F.
Lechat
F.
Woussidjeine
D.
and
Perly
B
, Abstract of Papers, 5th International Symposium on Cyclodextrins, Paris (1990 ), p. 31 .
35.
Ishizuka
Y.
Nagawa
Y.
Nakanishi
H.
and
Kuboyama
A
, J. Incl. Phenom. 9 , 219 (1990 ).
36.
Han
S. M.
Atkinson
W. M.
and
Purdie
N
, Anal. Chem. 56 , 2827 (1984 ).
37.
Bowen
J. M.
and
Purdie
N
, Anal. Chem. 53 , 2239 (1981 ).
38.
Schuette
J. M.
Ndou
T. T.
Muñoz de la Peña
A.
Greene
K. L.
Williamson
C.
and
Warner
I. M
, J. Phys. Chem. 95 , 4897 (1991 ).