[en] cyclodextrins ; drug modified release ; gel ; lipid vesicle solubilization ; liposomes
[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.