LIPOSOMES DISPERSED WITHIN A THERMOSENSITIVE GEL - A NEW DOSAGE FORM FOR OCULAR DELIVERY OF OLIGONUCLEOTIDES

Purpose. The main goal of this study was to develop an ocular controll ed release formulation of a model oligonucleotide (pdT16), contained w ithin liposomes dispersed within a thermosensitive eel composed by pol axamer 407. Methods. The influence of the poloxamer concentration 2% o r 27% on the stability of the liposomes IPC: CHOL and PC: CHOL: PEG-DS PE) was investigated. The in vitro release profiles of pdT16 from vari ous poloxamer formulations (free: pdT16 dispersed within 20% and 27% p oloxamer gels, pdTl6 encapsulated within liposomes dispersed within 20 % and 27% poloxamer gels;) were realized using a membrane-free release model. Results. The dispersion of liposomes within a dilute 2% poloxa mer solution resulted in a great leakage of pdT16 From liposomes. Howe ver, the destabilization effect of poloxamer was reduced when higher c oncentration (27%) was used. Poloxamer dissolution was found to contro l the release process of pdT16, whereas the dispersion of liposomes wi thin 27% poloxamer gel was shown to slow down the diffusion of pdT16 o ut from the gel. Conclusions. The dispersion of liposomes within a 27% poloxamer gel presented an interesting system to control the release of a model oligonucleotide compare to a simple gel.