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  • Title: Structural effects caused by spray- and freeze-drying of liposomes and bilayer disks.
    Author: Wessman P, Edwards K, Mahlin D.
    Journal: J Pharm Sci; 2010 Apr; 99(4):2032-48. PubMed ID: 19894278.
    Abstract:
    Cryo-TEM and dynamic light scattering was used to investigate morphological changes induced by spray- and freeze-drying of liposomes and nanosized bilayer disks composed of 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), cholesterol, and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-5000] (DSPE-PEG) 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. Uni-lamellar liposomes tended to shrink in size and become bi-lamellar 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 uni- to bi-lamellar structures. PEGylation promoted formation of larger liposomes during spray-drying, and had a similar, but less pronounced, effect also during freeze-drying. 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 spray- and freeze-drying, but the drying procedure did not change the open single-bilayer structure of the disks.
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