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 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. CONCLUSION: 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.
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 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. CONCLUSION: 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.
Authors: E P Kilsdonk; P G Yancey; G W Stoudt; F W Bangerter; W J Johnson; M C Phillips; G H Rothblat Journal: J Biol Chem Date: 1995-07-21 Impact factor: 5.157