Cyclodextrin-mediated drug release from liposomes dispersed within a bioadhesive gel.
OBJECTIVE
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 PEG-ylated liposomes and its release was measured in the presence of Me(beta)CD after vesicle dispersion within the bioadhesive Carbopol 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 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-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.


CONCLUSIONS
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.
Boulmedarat
Laïla
L
UMR CNRS 8612, School of Pharmacy, University of Paris-Sud, Châtenay-Malabry, France.
Piel
Géraldine
G
Bochot
Amélie
A
Lesieur
Sylviane
S
Delattre
Luc
L
Fattal
Elias
E
D000180:Acrylic Resins; D000269:Adhesives; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004339:Drug Compounding; D005614:Freeze Fracturing; D005615:Freezing; D005782:Gels; D007444:Inulin / Q000008:administration & dosage / Q000493:pharmacokinetics; D008051:Lipid Bilayers; D008081:Liposomes; D008854:Microscopy, Electron; D009391:Nephelometry and Turbidimetry; D004364:Pharmaceutical Preparations / Q000008:administration & dosage*; D011145:Polyvinyls; D012995:Solubility; D047392:beta-Cyclodextrins / Q000737:chemistry*
D000180:Acrylic Resins; D000269:Adhesives; D005782:Gels; D008051:Lipid Bilayers; D008081:Liposomes; D004364:Pharmaceutical Preparations; D011145:Polyvinyls; D047392:beta-Cyclodextrins; C108732:methyl-beta-cyclodextrin; C006912:carboxypolymethylene; D007444:Inulin