[en] It is well known that cyclodextrins are able to extract lipids constituting membranes, increasing their fluidity and permeability. This behaviour towards biological membranes is directly linked to the toxicological effects of methylated cyclodextrins. However, confusion is currently made in the literature between the different methylated cyclodextrin derivatives. Moreover, a new methylated cyclodextrin derivative recently occurred in the market. the Crysmeb (R). We wanted to compare and understand the effect of the most currently used cyclodextrins on a model membrane. We studied the influence of natural cyclodextrins (beta CD and gamma CD), methylated derivatives (2,6-dimethyl-beta CD (Dimeb), 2,3,6-trimethyl-beta CD (Trimeb) and randomly methylated-beta CD (Rameb), as well as the new derivative Crysmeb), hydroxypropylated derivatives (HP beta CD of different substitution degrees and HP gamma CD) and the sulfobutylated derivative (SBE beta CD) on the release of a fluorescent marker encapsulated in the inner cavity of liposomes. It was shown that the observed effect on calcein release can be directly related to the affinity of cyclodextrins for both lipid components of liposomes, cholesterol and phosphatidylcholine. From this relationship, we were able to determine, for each cyclodextrin, a theoretical concentration giving rise to 50% or 100% calcein release. This theoretical concentration was confirmed experimentally. We have also showed that cyclodextrins which provoke calcein release also induce large structure modifications of liposomes. (c) 2007 Elsevier B.V. All rights reserved.
Disciplines :
Pharmacy, pharmacology & toxicology
Author, co-author :
Piel, Géraldine ; Université de Liège - ULiège > Département de pharmacie > Pharmacie galénique et magistrale
Piette, Marie ; Université de Liège - ULiège > Département de pharmacie > Pharmacie galénique
Barillaro, Valery
Castagne, Delphine ; Université de Liège - ULiège > Département de pharmacie > Pharmacie galénique et magistrale
Evrard, Brigitte ; Université de Liège - ULiège > Département de pharmacie > Pharmacie galénique
Delattre, Luc ; Université de Liège - ULiège > Département de pharmacie > Département de pharmacie
Language :
English
Title :
Study of the relationship between lipid binding properties of cyclodextrins and their effect on the integrity of liposomes
Anderson T.G., Tan A., Ganz P., and Seelig J. Calorimetric measurement of phospholipid interaction with methyl-beta-cyclodextrin. Biochemistry 43 (2004) 2251-2261
Asai K., Morishita M., Katsuta H., Hosoda S., Shinomiya K., Noro M., Nagai T., and Takayama K. The effects of water-soluble cyclodextrins on the histological integrity of the rat nasal mucosa. Int. J. Pharm. 246 (2002) 25-35
Boulmedarat L., Piel G., Bochot A., Lesieur S., Delattre L., and Fattal E. Cyclodextrin-mediated drug release from liposomes dispersed within a bioadhesive gel. Pharmacol. Res. 22 (2005) 962-971
Chavanpatil M.D., and Vavia P.R. The influence of absorption enhancers on nasal absorption of acyclovir. Eur. J. Pharm. Biopharm. 57 (2004) 483-487
Fatouros D.G., Hatzidimitriou K., and Antimisiaris S.G. Liposomes encapsulating prednisolone and prednisolone-cyclodextrin complexes: comparison of membrane integrity and drug release. Eur. J. Pharm. Sci. 13 (2001) 287-296
Frijlink H.W., Eissens A.C., Hefting N.R., Poelstra K., Lerk C.F., and Meijer D.K. The effect of parenterally administered cyclodextrins on cholesterol levels in the rat. Pharmacol. Res. 8 (1991) 9-16
Giocondi M.C., Milhiet P.E., Dosset P., and Le Grimellec C. Use of cyclodextrin for AFM monitoring of model raft formation. Biophys. J. 86 (2004) 861-869
Hatzi P., Mourtas S., Klepetsanis P.G., and Antimisiaris S.G. Integrity of liposomes in presence of cyclodextrins: effect of liposome type and lipid composition. Int. J. Pharm. 333 (2007) 167-176
Higuchi T., and Connors K. Phase solubility techniques. Adv. Anal. Chem. Instrum. 4 (1965) 127-212
Irie T., and Uekama K. Cyclodextrins in peptide and protein delivery. Adv. Drug Deliv. Rev. 36 (1999) 101-123
Kilsdonk E.P., Yancey P.G., Stoudt G.W., Bangerter F.W., Johnson W.J., Phillips M.C., and Rothblat G.H. Cellular cholesterol efflux mediated by cyclodextrins. J. Biol. Chem. 270 (1995) 17250-17256
Kokkona M., Kallinteri P., Fatouros D., and Antimisiaris S.G. Stability of SUV liposomes in the presence of cholate salts and pancreatic lipases: effect of lipid composition. Eur. J. Pharm. Sci. 9 (2000) 245-252
Leroy-Lechat F., Wouessidjewe D., Andreux J.P., Puisieux F., and Duchêne D. Evaluation of the cytotoxicity of cyclodextrins and hydroxypropylated derivatives. Int. J. Pharm. 101 (1994) 97-103
Loftsson T., Hreinsdóttir D., and Másson M. Evaluation of cyclodextrin solubilization of drugs. Int. J. Pharm. 302 (2005) 18-28
Merkus F.W.H.M., Schipper N.G.M., and Verhoef J.C. The influence of absorption enhancers on intranasal insulin absorption in normal and diabetic subjects. J. Control. Rel. 41 (1996) 69-75
Nishijo J., and Mizuno H. Interactions of cyclodextrins with DPPC liposomes. Differential scanning calorimetry studies. Chem. Pharm. Bull. 46 (1998) 120-124
Nishijo J., Moriyama S., and Shiota S. Interactions of cholesterol with cyclodextrins in aqueous solution. Chem. Pharm. Bull. 51 (2003) 1253-1257
Nishijo J., Moriyama S., Shiota S., Kamigauchi M., and Sugiura M. Interaction of heptakis (2,3,6-tri-O-methyl)-beta-cyclodextrin with cholesterol in aqueous solution. Chem. Pharm. Bull. 52 (2004) 1405-1410
Nishijo J., Shiota S., Mazima K., Inoue Y., Mizuno H., and Yoshida J. Interactions of cyclodextrins with dipalmitoyl, distearoyl, and dimyristoyl phosphatidyl choline liposomes. A study by leakage of carboxyfluorescein in inner aqueous phase of unilamellar liposomes. Chem. Pharm. Bull. 48 (2000) 48-52
Ohvo H.B., Åkerlund, and Slotte J.P. Cyclodextrin-catalyzed extraction of fluorescent sterols from monolayer membranes and small unilamellar vesicles. Chem. Phys. Lipid 105 (2000) 167-178
Ohvo H., and Slotte J.P. Cyclodextrin-mediated removal of sterols from monolayers: effects of sterol structure and phospholipids on desorption rate. Biochemistry 35 (1996) 8018-8024
Piel G., Piette M., Barillaro V., Castagne D., Evrard B., and Delattre L. Betamethasone-in-cyclodextrin-in-liposome: the effect of cyclodextrins on encapsulation efficiency and release kinetics. Int. J. Pharm. 312 (2006) 75-82
Redenti E., Pietra C., Gerloczy A., and Szente L. Cyclodextrins in oligonucleotide delivery. Adv. Drug Deliv. Rev. 53 (2001) 235-244
Schnitzer E., Kozlov M.M., and Lichtenberg D. The effect of cholesterol on the solubilization of phosphatidylcholine bilayers by the non-ionic surfactant Triton X-100. Chem. Phys. Lipid 135 (2005) 69-82
Williams R., Mahaguna V., and Sriwongjanya M. Characterization of an inclusion complex of cholesterol and hydroxypropyl-β-cyclodextrin. Eur. J. Pharm. Biopharm. 46 (1998) 355-360
Yancey P.G., Rodrigueza W.V., Kilsdonk E.P., Stoudt G.W., Johnson W.J., Phillips M.C., and Rothblat G.H. Cellular cholesterol efflux mediated by cyclodextrins. Demonstration of kinetic pools and mechanism of efflux. J. Biol. Chem. 271 (1996) 16026-16034