Steam sterilisation of vesicular phospholipid gels

Vesicular phospholipid gels (VPGs), highly concentrated phospholipid disper sions of semisolid consistency and vesicular morphology are under investiga tion as potential implantable depots for sustained release of drugs and as intermediates for subsequent dilution into 'conventional" liposome dispersi ons. It was investigated here if VPGs can be steam sterilised. VPGs prepare d from 400 mg/g egg-phosphatidylcholine by high-pressure homogenisation ret ained their vesicular structure but showed a slight increase in vesicle siz e (freeze-fracture electron microscopy). However, autoclaving slowed down b oth, the in vitro release of the hydrophilic marker carboxyfluorescein and vesicles from VPGs. This was assumed to be due to bigger vesicle sizes and corresponding increase in packing density of the vesicular matrix. Upon dil ution into a liposome dispersion both negative staining electron microscopy and dynamic laser light scattering analysis confirmed a distinct increase in liposome size, mainly due to fusion of small (20 nm) Vesicles with unfav ourable curvature. This was consistent with the observed increase in encaps ulation efficiency of carboxyfluorescein. Phospholipid hydrolysis during au toclaving was negligible with lysophosphatidylcholine formation of less tha n 2% (thin layer chromatography). Despite significant change of their morph ological and functional properties during autoclaving VPGs retained their m ain characteristics, such as vesicular structure, sustained release and dil utability to liposome dispersions, and are, therefore, considered as autocl avable. (C) 2001 Published by Elsevier Science B.V.