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Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
Size of thermosensitive liposomes influences content release.
J. Control. Release 147, 436-443 (2010)
Thermosensitive liposomes (TSL) in combination with regional hyperthermia represent a powerful tool for tumor specific drug delivery. The objective of this study was to investigate the influence of vesicle size on the biophysical properties of TSL TSL were composed of DPPC/DSPC/1,2-dipalmitoyl-sn-glycero-3-phosphoglyceroglycerol (DPPG(2)) 50:20:30 (mol/mol) (DPPG(2)-TSL) and DPPC/P-Lyso-PC/DSPE-PEG2000 90:10:4 (mol/mol) (PEG/Lyso-TSL) with encapsulated fluorescent dye carboxyfluorescein, anticancer drug doxorubicin or magnetic resonance contrast agent gadodiamide. Extrusion was performed with polycarbonate filters of distinct pore size to obtain TSL with different diameters (50 to 200 nm). Phase transition temperature (T-m) of the bilayer forming phospholipids was not influenced by vesicle size in the tested range. However, vesicle size had a major impact on in vitro content release properties of TSL in the investigated temperature range between 30 and 45 degrees C. Generally, vesicle size was inversely related to content release properties with increased content release rates for decreased vesicle sizes. Size dependency of content release properties varied between all tested formulations and DPPG(2)-TSL were generally less affected by size changes in the range of 100 to 150 nm as compared to PEG/Lyso-TSL. Independent from gadodiamide release, vesicle size influenced the signal intensity of DPPG(2)-TSL also at temperatures below T-m due to improved water exchange for smaller vesicles. Liposomes around 100 nm in size are routinely used in vivo, hence a quality control for TSL preparations is required prior to use. Even small changes in size or a wider size distribution might affect stability and release properties and thus yield in decreased efficacy or unwanted side effects of drug loaded TSL during in vivo applications.
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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
Thermosensitive liposomes; Vesicle size; Phosphatidyloligoglycerol; Drug delivery; Hyperthermia
ISSN (print) / ISBN
0168-3659
e-ISSN
1873-4995
Zeitschrift
Journal of Controlled Release
Quellenangaben
Band: 147,
Heft: 3,
Seiten: 436-443
Verlag
Elsevier
Nichtpatentliteratur
Publikationen
Begutachtungsstatus
Peer reviewed
Institut(e)
CCG Tumor Therapy with Hyperthermia (IMI-KTH)