Liposomes dispersed within a thermosensitive gel: a new dosage form for ocular delivery of oligonucleotides.
OBJECTIVE
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 gel composed by poloxamer 407.


METHODS
The influence of the poloxamer concentration 2% or 27% on the stability of the liposomes (PC: 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, pdT16 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.
Bochot
A
A
Laboratoire de Physico-Chimie, Pharmacotechnie, Biopharmacie, URA CNRS 1218, Faculté de Pharmacie, Châtenay-Malabry, France.
Fattal
E
E
Gulik
A
A
Couarraze
G
G
Couvreur
P
P
D004337:Drug Carriers; D016503:Drug Delivery Systems; D005079:Excipients; D006531:HEPES; D006801:Humans; D066298:In Vitro Techniques; D008081:Liposomes; D008954:Models, Biological; D009799:Ocular Physiological Phenomena; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage* / Q000737:chemistry; D009883:Ophthalmic Solutions; D020442:Poloxamer; D012995:Solubility
D004337:Drug Carriers; D005079:Excipients; D008081:Liposomes; D016376:Oligonucleotides, Antisense; D009883:Ophthalmic Solutions; D020442:Poloxamer; D006531:HEPES