Characterization of a new ocular delivery system based on a dispersion of liposomes in a thermosensitive gel

This paper describes a novel approach for designing an ocular delivery system based on the dispersion of liposomes into a thermosensitive gel made of a copolymer of ethylene oxide and propylene oxide (poloxamer 407). Ar high copolymer concentrations (20-30%), and from a temperature of approximately 20 degrees C, poloxamer 407 passes from a solution to a gel. In order to stabilize liposomes in the gel, PEG2000-DSPE was introduced in their composition. Adsorption studies investigated by size and zeta-potential measurements have shown that the adsorption was higher for positively charged or neutral non-sterically stabilized liposomes. Poloxamer 407 adsorbed to a lower extent with negatively charged or PEG-DSPE containing liposomes. Furthermore, using a fluorescent aqueous marker, it was shown that liposome permeability was dramatically reduced in the presence of poloxamer 407 when PEG-DSPE was incorporated into the liposomes. This data suggests that poloxamer 407 could adsorb, at different extents, to all types of vesicles bur that bilayer destabilization by the copolymer was reduced when liposomes were sterically stabilized. This was explained by the poor accessibility of the poloxamer to the phospholipidic which is the possible consequence of the steric repulsion effect induced by polyethylene glycol. Finally, it was shown that the thermosensitivity of poloxamer 407 was maintained after introducing the liposomes into the gel. In conclusion, a new system based on a dispersion of peggylated liposomes into thermosensitive poloxamer 407 is proposed, offering new potentialities for delivery of drugs. (C) 1998 Elsevier Science B.V. All rights reserved.