title: The effect of aging on the physical stability of liposome dispersions.
abstract: In this study, the effect of aging, in terms of hydrolytic decomposition of the bilayer forming (phospho)lipids, on the physical stability of aqueous liposome dispersion was investigated in partially hydrogenated egg phosphatidylcholine (PHEPC) and egg phosphatidylglycerol (EPG) containing liposomes with or without cholesterol. The physical stability of the liposome dispersions was assessed by measuring the leak-in rate of a non-bilayer interacting hydrophilic marker molecule, calcein and changes in the particle size and its distribution in time. Additionally, permeability of either partially hydrolysed phospholipids or exogenous lyso-phosphatidylcholine(LPC) containing bilayers was calculated. The experiments were performed at 40 degrees C. Liposome dispersions were aged artificially by storing at 60 degrees C. The size of the liposomes and polydispersity index of the dispersions, in general, did not change significantly. The leak-in rate of calcein in externally added LPC containing liposomes was increased relative to the incorporated LPC concentration. The higher the LPC content of the bilayers, the higher the leak-in rate of calcein into liposomes. The leak-in rate of calcein, however, decreased first in partially hydrolysed phospholipids containing liposomes up to around 10% of hydrolysis and, afterwards, it started to increase. The leak-in rate was always lower in partially hydrolysed phospholipids containing liposomes than externally added LPC containing ones. Furthermore, the permeability of cholesterol containing bilayers was also always lower than the bilayers without cholesterol. In conclusion, addition of LPC into liposomal bilayers increases the permeability of bilayer. However, bilayers containing the hydrolysis products of phospholipids, both lyso-phospholipids and free fatty acids, did not show any enhanced permeability up to around 15% hydrolysis. Bilayer permeability is enhanced above 15% hydrolysis.
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmacy, University of Utrecht, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Grit
authors.forename: D J
authors.initials: DJ
authors.lastname: Crommelin
mesh_terms: D002784:Cholesterol; D004355:Drug Stability; D005452:Fluoresceins; D006868:Hydrolysis; D008051:Lipid Bilayers; D008081:Liposomes; D010539:Permeability; D010713:Phosphatidylcholines; D010715:Phosphatidylglycerols; D013997:Time Factors
chemical_list: D005452:Fluoresceins; D008051:Lipid Bilayers; D008081:Liposomes; D010713:Phosphatidylcholines; D010715:Phosphatidylglycerols; D002784:Cholesterol; C007740:fluorexon