Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2485118 | Journal of Pharmaceutical Sciences | 2010 | 17 Pages |
Abstract
CryoâTEM and dynamic light scattering was used to investigate morphological changes induced by sprayâ and freezeâdrying of liposomes and nanosized bilayer disks composed of 1,2âdistearoylâsnâglyceroâ3âphosphocholine (DSPC), cholesterol, and 1,2âdistearoylâsnâglyceroâ3âphosphoethanolamineâNâ[methoxy(polyethylene glycol)â5000] (DSPEâPEG) from lactose solution. Particular focus was put on the identification of structural alterations that risk influencing the performance of liposomes and bilayer disks as carriers for protein and peptide drugs. Significant changes in the lipid aggregate structure and/or size was noted upon dehydration. Uniâlamellar liposomes tended to shrink in size and become biâlamellar as a consequence of the drying process. The same transformation was observed upon deliberate establishment of a lactose gradient over the membranes of liposomes in solution. A mechanism based on an osmotically driven invagination of the liposomes is proposed to explain the change from uniâ to biâlamellar structures. PEGylation promoted formation of larger liposomes during sprayâdrying, and had a similar, but less pronounced, effect also during freezeâdrying. The observed structural changes may have important consequences for the bioavailability of protein/peptide drugs bound to, or embedded in, the liposome membranes. The radius of bilayer disks increased upon both sprayâ and freezeâdrying, but the drying procedure did not change the open singleâbilayer structure of the disks. © 2009 WileyâLiss, Inc. and the American Pharmacists Association J Pharm Sci 99: 2032-2048, 2010
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Authors
Per Wessman, Katarina Edwards, Denny Mahlin,