title: Betamethasone-in-cyclodextrin-in-liposome: the effect of cyclodextrins on encapsulation efficiency and release kinetics.
abstract: Lipophilic drugs have limited solubility in phospholipid systems, hence maximum entrapment levels in liposomes are known to be low. "Drugs-in-cyclodextrin-in-liposome" systems were previously proposed to overcome this drawback but studies were limited to betaCD and HPbetaCD. In some cases, other cyclodextrins may be more interesting than betaCD or HPbetaCD, such as methylated cyclodextrins. However, these cyclodextrins are known to extract lipid components from the lipid membrane, which may destabilize liposomes. We tested the influence of several cyclodextrins (betaCD, gammaCD, Dimeb, Trimeb, Crysmeb, Rameb, HPbetaCD and HPgammaCD) on the aqueous solubility of betamethasone by phase solubility diagrams and on the encapsulation efficiency in liposomes. The release kinetics of betamethasone was studied using Franz diffusion cells. We showed that release kinetics are directly correlated with encapsulation efficiency, which is closely related to betamethasone concentration in cyclodextrin complex solution. No liposome destruction was observed, even with the testing of methylated cyclodextrins at the highest concentration (40 mM). This can be explained by the fact that these cyclodextrins have a higher affinity for betamethasone than for cholesterol. This was proved by the comparison of phase solubility diagrams of both betamethasone and cholesterol.
authors.affiliation: Laboratory of Pharmaceutical Technology, Department of Pharmacy, University of Liège, CHU, Tour 4, Bat B36, 1 Avenue de l'Hopital, 4000 Liège, Belgium. Geraldine.piel@ulg.ac.be
authors.forename: Géraldine
authors.initials: G
authors.lastname: Piel
authors.forename: Marie
authors.initials: M
authors.lastname: Piette
authors.forename: Valery
authors.initials: V
authors.lastname: Barillaro
authors.forename: Delphine
authors.initials: D
authors.lastname: Castagne
authors.forename: Brigitte
authors.initials: B
authors.lastname: Evrard
authors.forename: Luc
authors.initials: L
authors.lastname: Delattre
mesh_terms: D000588:Amines / Q000737:chemistry; D001623:Betamethasone / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D002784:Cholesterol / Q000737:chemistry; D003505:Cyclodextrins / Q000737:chemistry*; D005614:Freeze Fracturing; D005782:Gels; D007700:Kinetics; D008081:Liposomes; D046529:Microscopy, Electron, Transmission; D010316:Particle Size; D010713:Phosphatidylcholines / Q000737:chemistry; D012995:Solubility; D014867:Water
chemical_list: D000588:Amines; D003505:Cyclodextrins; D005782:Gels; D008081:Liposomes; D010713:Phosphatidylcholines; D014867:Water; D002784:Cholesterol; D001623:Betamethasone; C009317:stearylamine