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 controlled release formulation of a model oligonucleotide (pdT16), contained within liposomes dispersed within a thermosensitive eel composed by polaxamer 407. Methods. The influence of the poloxamer concentration 2% or 27% on the stability of the liposomes IPC: CHOL and PC: CHOL: PEG-DSPE) was investigated. The in vitro release profiles of pdT16 from various poloxamer formulations (free: pdT16 dispersed within 20% and 27% poloxamer 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% poloxamer solution resulted in a great leakage of pdT16 From liposomes. However, the destabilization effect of poloxamer was reduced when higher concentration (27%) was used. Poloxamer dissolution was found to control the release process of pdT16, whereas the dispersion of liposomes within 27% poloxamer gel was shown to slow down the diffusion of pdT16 out 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.