Formation of eLiposomes as a drug delivery vehicle

• Published in: Colloids and surfaces, B, Biointerfaces B, Biointerfaces, 2012-01, Vol.89 (1), p.93-100
• Main Authors: Lattin, J.R., Belnap, D.M., Pitt, W.G.
• Format: Article
• Language: English
• Subjects: 1,2-Dipalmitoylphosphatidylcholine - chemistry; centrifugation; choline; colloids; Cryo-electron microscopy; Droplets; drug carriers; Drug delivery; Drug Delivery Systems; Drugs; Emulsion; Emulsions; encapsulation; Ethanol; Ethyl alcohol; Extrusion; filters; image analysis; Liposome; Liposomes; Microscopy, Electron, Transmission; Perfluorocarbon; permeability; SUV; transmission electron microscopy; ultrasonics; Ultrasound; washing
• ISSN: 0927-7765; 1873-4367
• DOI: 10.1016/j.colsurfb.2011.08.030

[Display omitted] ► Perfluorocarbon emulsions were formed by sonication and stabilized with DPPC. ► Emulsion size could be reduced to 50nm or 100nm by extrusion through a filter. ► Emulsion droplets were encapsulated in liposomes by the refolding of lipid sheets. ► The size of the resulting eLiposomes could also be controlled by extrusion. This paper discusses the formation of eLiposomes, defined as a liposome with internal emulsion droplets. Liposomes have been investigated as passively targeted drug carriers due to their ability to deliver drugs to a cancerous tumor via the enhanced permeability and retention (EPR) effect. The enclosed emulsion droplets in an eLiposome add the ability to further control the location and time of release from the liposome with ultrasound. Emulsion droplets were formed from perfluorohexane (PFC6) by sonication at 20kHz and stabilized with dipalmitoyl phosphatidyl choline (DPPC). The size of the resulting droplets was reduced to approximately 100nm or 50nm by extrusion through polycarbonate filters of the same size at 50°C. Small unilamellar vesicles (SUVs) were prepared from DPPC by thin film hydration and extrusion through a 50nm filter. Interdigitated DPPC sheets were prepared from the SUVs by the addition of ethanol to a concentration of 3M. Excess ethanol was removed by centrifugation washing. The sheets were mixed with emulsion and the solution was heated to 50°C, resulting in the refolding of the DPPC sheets into closed vesicles. Emulsion droplets were encapsulated inside of the newly formed eLiposomes. The size of the eLiposomes was reduced by extrusion. Cryogenic transmission electron microscopy (cryoTEM) and negative-staining TEM were used to image the emulsion droplets and the eLiposomes. Encapsulation of emulsion droplets was verified by rotating the microscope stage of cryoTEM samples.