title: Size of thermosensitive liposomes influences content release.
abstract: 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 200nm). 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°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 150nm 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 100nm 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.
authors: Department of Internal Medicine III, University Hospital Grosshadern, Ludwig-Maximilians University, Munich, Germany. Martin.Hossann@med.uni-muenchen.de
authors: Martin
authors: M
authors: Hossann
authors: Tungte
authors: T
authors: Wang
authors: Michael
authors: M
authors: Wiggenhorn
authors: Rebecca
authors: R
authors: Schmidt
authors: Anja
authors: A
authors: Zengerle
authors: Gerhard
authors: G
authors: Winter
authors: Hansjörg
authors: H
authors: Eibl
authors: Michael
authors: M
authors: Peller
authors: Maximilian
authors: M
authors: Reiser
authors: Rolf D
authors: RD
authors: Issels
authors: Lars H
authors: LH
authors: Lindner
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D003287:Contrast Media / Q000737:chemistry*; D004317:Doxorubicin / Q000008:administration & dosage / Q000737:chemistry*; D004339:Drug Compounding; D005452:Fluoresceins / Q000737:chemistry*; D005456:Fluorescent Dyes / Q000737:chemistry*; D019786:Gadolinium DTPA / Q000737:chemistry*; D006801:Humans; D006979:Hyperthermia, Induced; D007700:Kinetics; D008081:Liposomes; D009682:Magnetic Resonance Spectroscopy; D036103:Nanotechnology; D010316:Particle Size; D010539:Permeability; D010743:Phospholipids / Q000737:chemistry*; D012995:Solubility; D013499:Surface Properties; D013678:Technology, Pharmaceutical / Q000379:methods; D013696:Temperature
chemical_list: D000903:Antibiotics, Antineoplastic; D003287:Contrast Media; D005452:Fluoresceins; D005456:Fluorescent Dyes; D008081:Liposomes; D010743:Phospholipids; C024098:6-carboxyfluorescein; D004317:Doxorubicin; C064925:gadodiamide; D019786:Gadolinium DTPA