Cyclodextrin-mediated drug release from liposomes dispersed within a bioadhesive gel

[en] Purpose. The aim of the present study was to design a new mucosal drug delivery system composed of liposomes dispersed within a bioadhesive hydrogel containing methyl-beta-cyclodextrin (Me beta CD) for controlled drug release. Methods. A hydrophilic model molecule, inulin, was encapsulated within positively charged and PEGylated liposomes and its release was measured in the presence of Me beta CD after vesicle dispersion within the bioadhesive Carbopol(R) 974P gel. Freeze-fracture electron microscopy (FFEM) was used to follow liposome morphological changes when dispersed within the hydrogel. Liposome- Me beta CD interactions were investigated by turbidity monitoring during continuous addition of Me beta CD to liposomes and by FFEM. Results. Inulin diffusion within the gel was influenced by Carbopol(R) 974P concentration since no gel erosion occurred. When dispersed within the gel, positively charged liposomes displayed a higher stability than PEG-ylated vesicles. In the presence of Me beta CD, higher amounts of free inulin were released from liposomes, especially in Carbopol(R)-free system. Me beta CD appeared to diffuse towards lipid vesicles and permeabilized their bilayer allowing inulin leakage. Indeed, freeze-fracture experiments and liposome turbidity monitoring have shown that Me beta CD behaved as a detergent behavior, resulting in lipid vesicle solubilization. Conclusion. Me beta CD is able to mediate, within a bioadhesive hydrogel, the release of a liposome-encapsulated molecule allowing further application of this delivery system for mucosal administration.

Disciplines :

Pharmacy, pharmacology & toxicology
Chemistry

Author, co-author :

Piel, Géraldine ; Université de Liège - ULiège > Département de pharmacie > Pharmacie galénique

Boulmedarat, Laila

Bochot, Amelie

Lesieur, Sylviane

Delattre, Luc ; Université de Liège - ULiège > Département de pharmacie > Département de pharmacie

Fattal, Elias

Language :

English

Title :

Cyclodextrin-mediated drug release from liposomes dispersed within a bioadhesive gel

Publication date :

June 2005

Journal title :

Pharmaceutical Research

ISSN :

0724-8741

eISSN :

1573-904X

Publisher :

Springer/Plenum Publishers, New York, United States - New York

Volume :

Issue :

Pages :

962-971

Peer reviewed :

Peer Reviewed verified by ORBi

Available on ORBi :

since 13 August 2009

Statistics

Number of views

110 (9 by ULiège)

Number of downloads

5 (2 by ULiège)

More statistics

Scopus citations^®

Scopus citations^®
without self-citations

OpenCitations

Bibliography

De Vries, M.E., Bodde, H.E., Verhoef, J.C., Junginger, H.E., Developments in buccal drug delivery (1991) Crit. Rev. Ther. Drug Carr. Syst., 8, pp. 271-303
Garren, K.W., Repta, A.J., Buccal drug absorption. I. Comparative levels of esterase and peptidase activities in rat and hamster buccal and intestinal homogenates (1988) Int. J. Pharm., 48, pp. 189-194
Sarkar, M.A., Drug metabolism in the nasal mucosa (1992) Pharm. Res., 9, pp. 1-9
Woodley, J.F., Enzymatic barriers for GI peptide and protein delivery (1994) Crit. Rev. Ther. Drug Carr. Syst., 11, pp. 61-95
Squier, C., The permeability of oral mucosa (1991) Crit. Rev. Oral Biol. Med., 2, pp. 13-32
Arora, P., Sharma, S., Garg, S., Permeability issues in nasal drug delivery (2002) Drug Discov. Today, 7, pp. 967-975
Rathbone, M.J., Hadgraft, J., Absorption of drugs from the human oral cavity (1991) Int. J. Pharm., 74, pp. 9-24
Harris, D., Robinson, J.R., Drug delivery via the mucous membranes of the oral cavity (1992) J. Pharm. Sci., 81, pp. 1-10
Harris, D., Robinson, J.R., Bioadhesive polymers in peptide drug delivery (1990) Biomaterials, 11, pp. 652-658
Niesman, M.R., The use of liposomes as drug carriers in ophthalmology (1992) Crit. Rev. Ther. Drug Carr. Syst., 9, pp. 1-38
Pavelic, Z., Skalko-Basnet, N., Jalsenjak, I., Liposomes containing drugs for treatment of vaginal infections (1999) Eur. J. Pharm. Sci., 8, pp. 345-351
Senel, S., Hincal, A.A., Drug permeation enhancement via buccal route: Possibilities and limitations (2001) J. Control. Release, 72, pp. 133-144
Sveinsson, S.J., Peter Holbrook, W., Oral mucosal adhesive ointment containing liposomal corticosteroid (1993) Int. J. Pharm., 95, pp. 105-109
Shao, Z., Krishnamoorthy, R., Mitra, A.K., Cyclodextrins as nasal absorption promoters of insulin: Mechanistic evaluations (1992) Pharm. Res., 9, pp. 1157-1163
Schipper, N.G., Verhoef, J.C., De Lannoy, L.M., Romeijn, S.G., Brakkee, J.H., Wiegant, V.M., Gispen, W.H., Merkus, F.W., Nasal administration of an ACTH(4-9) peptide analogue with dimethyl-beta-cyclodextrin as an absorption enhancer: Pharmacokinetics and dynamics (1993) Br. J. Pharmacol., 110, pp. 1335-1340
Verhoef, J.C., Schipper, N.G.M., Romeijn, S.G., Merkus, F.W.H.M., The potential of cyclodextrins as absorption enhancers in nasal delivery of peptide drugs (1994) J. Control. Release, 29, pp. 351-360
Steward, A., Bayley, D.L., Howes, C., The effect of enhancers on the buccal absorption of hybrid (BDBB) [alpha]-interferon (1994) Int. J. Pharm., 104, pp. 145-149
Matsubara, K., Abe, K., Irie, T., Uekama, K., Improvement of nasal bioavailability of luteinizing hormone-releasing hormone agonist, buserelin, by cyclodextrin derivatives in rats (1995) J. Pharm. Sci., 84, pp. 1295-1300
Marttin, E., Verhoef, J.C., Merkus, F.W., Efficacy, safety and mechanism of cyclodextrins as absorption enhancers in nasal delivery of peptide and protein drugs (1998) J. Drug Target., 6, pp. 17-36
Irie, T., Uekama, K., Cyclodextrins in peptide and protein delivery (1999) Adv. Drug Deliv. Rev., 36, pp. 101-123
Kilsdonk, E.P.C., Johnson, W.J., Rothblat, G.H., Bangerter, F.W., Cyclodextrin-mediated efflux of cellular cholesterol (1995) Atherosclerosis, 115, p. 100
Ohtani, Y., Irie, T., Uekama, K., Fukunaga, K., Pitha, J., Differentialeffectsof[alpha]-, [beta]- and [gamma]-cyclodextrins on human erythrocytes (1989) Eur. J. Biochem., 186, pp. 17-22
Irie, T., Uekama, K., Pharmaceutical applications of cyclodextrins. III. Toxicological issues and safety evaluation (1997) J. Pharm. Sci., 86, pp. 147-162
Bangham, A.D., Standish, M.M., Watkins, J.C., Diffusion of univalent ions across the lamellae of swollen phospholipids (1965) J. Mol. Biol., 13, pp. 238-252
Takayama, M., Itoh, S., Nagasaki, T., Tanimizu, I., A new enzymatic method for determination of serum choline-containing phospholipids (1977) Clin. Chim. Acta, 79, pp. 93-98
Bochot, A., Fattal, E., Gulik, A., Couarraze, G., Couvreur, P., Liposomes dispersed within a thermosensitive gel: A new dosage form for ocular delivery of oligonucleotides (1998) Pharm. Res., 15, pp. 1364-1369
Ramaldes, G.A., Fattal, E., Puisieux, F., Ollivon, M., Solubilization kinetics of phospholipid vesicles by sodium taurocholate (1996) Colloids Surf B: Biointerfaces, 6, pp. 363-371
Lesieur, S., Ollivon, M., Uchegbu, I.F., (2000) Non-ionic Surfactant Vesicle to Micelle Transition, pp. 49-79. , Harwood Academic Publishers Amsterdam
Lichtenberg, D., Robson, R.J., Dennis, E.A., Solubilization of phospholipids by detergents. Structural and kinetic aspects (1983) Biochim. Biophys. Acta, 737, pp. 285-304
Ollivon, M., Eidelman, O., Blumenthal, R., Walter, A., Micelle-vesicle transition of egg phosphatidylcholine and octyl glucoside (1988) Biochemistry, 27, pp. 1695-1703
Paternostre, M.T., Roux, M., Rigaud, J.L., Mechanisms of membrane protein insertion into liposomes during reconstitution procedures involving the use of detergents. 1. Solubilization of large unilamellar liposomes (prepared by reverse-phase evaporation) by triton X-100, octyl glucoside, and sodium cholate (1988) Biochemistry, 27, pp. 2668-2677
Paternostre, M., Meyer, O., Grabielle-Madelmont, C., Lesieur, S., Ghanam, M., Ollivon, M., Partition coefficient of a surfactant between aggregates and solution: Application to the micelle-vesicle transition of egg phosphatidylcholine and octyl beta-D-glucopyranoside (1995) Biophys. J., 69, pp. 2476-2488
Tirosh, O., Barenholz, Y., Katzhendler, J., Priev, A., Hydration of polyethylene glycol-grafted liposomes (1998) Biophys. J., 74, pp. 1371-1379
Senior, J., Delgado, C., Fisher, D., Tilcock, C., Gregoriadis, G., Influence of surface hydrophilicity of liposomes on their interaction with plasma protein and clearance from the circulation: Studies with poly(ethylene glycol)-coated vesicles (1991) Biochim. Biophys. Acta, 1062, pp. 77-82
Torchilin, V.P., Papisov, M.I., Why do polyethylene glycol-coated liposomes circulate so long? (1994) J. Liposome Res., 4, pp. 725-739
Frijlink, H.W., Eissens, A.C., Hefting, N.R., Poelstra, K., Lerk, C.F., Meijer, D.K., The effect of parenterally administered cyclodextrins on cholesterol levels in the rat (1991) Pharm. Res., 8, pp. 9-16
Leroy-Lechat, F., Wouessidjewe, D., Andreux, J.-P., Puisieux, F., Duchene, D., Evaluation of the cytotoxicity of cyclodextrins and hydroxypropylated derivatives (1994) Int. J. Pharm., 101, pp. 97-103
Kilsdonk, E.P., Yancey, P.G., Stoudt, G.W., Bangerter, F.W., Johnson, W.J., Phillips, M.C., Rothblat, G.H., Cellular cholesterol efflux mediated by cyclodextrins (1995) J. Biol. Chem., 270, pp. 17250-17256
Yancey, P.G., Rodrigueza, W.V., Kilsdonk, E.P., Stoudt, G.W., Johnson, W.J., Phillips, M.C., Rothblat, G.H., Cellular cholesterol efflux mediated by cyclodextrins. Demonstration of kinetic pools and mechanism of efflux (1996) J. Biol. Chem., 271, pp. 16026-16034
Boulmedarat, L., Bochot, A., Perly, B., Lesieur, L., Fattal, E., (2004) Solubilizing Effects of Methyl-b-cyclodextrin Toward Liposomes Involving a Detergent Like Mechanism, , Submitted
Lesieur, S., Grabielle-Madelmont, C., Ménager, C., Cabuil, V., Dadhi, D., Pierrot, P., Edwards, K., Evidence of surfactant-induced formation of transient pores in lipid bilayers by using magnetic-fluid-loaded liposomes (2003) J. Am. Chem. Soc., 125, pp. 5266-5267