title: Investigations of the influence of liposome composition on vesicle stability and drug transfer in human plasma: a transfer study.
abstract: Liposomal delivery constitutes a promising approach for i.v. administration of temoporfin (mTHPC) because lipid membranes can host these drug molecules. This study investigates the transfer and release of mTHPC to plasma proteins and stability of various liposomal formulations. To this end, we employed traces of radioactive markers and studied the effects of fatty acid chain length and the degree of saturation in the lipophilic tail, addition of cholesterol and PEGylation of the membrane surface and different drug-to-lipid ratios (DLRs). Liposomes were incubated in human plasma for various incubation times. Drawn samples were separated by asymmetrical flow field-flow fractionation (AF4). Drug was recovered in four fractions identified as albumin, high-density lipoprotein (HDL), low-density lipoprotein (LDL) and liposomes. Our results suggest that mTHPC fits best into fluid, unmodified bilayers when the drug-to-lipid ratio is low. Membrane rigidification as well as the presence of cholesterol and PEGyated lipids reduced the ability of the membrane to accommodate the drug but simultaneously improved the vesicle stability in plasma. Both mechanisms jointly affect the total degree of mTHPC release. We analyzed our data using a kinetic model that suggests the drug to be associated with the host membrane in two distinct states of which only one interacts directly with the plasma compartment.
authors.affiliation: a Department of Pharmaceutical Technology , Friedrich Schiller University Jena , Jena , Germany and.
authors.forename: Stephan
authors.identifier: http://orcid.org/0000-0001-8659-4070
authors.initials: S
authors.lastname: Holzschuh
authors.affiliation: a Department of Pharmaceutical Technology , Friedrich Schiller University Jena , Jena , Germany and.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Kaeß
authors.affiliation: b Department of Physics , North Dakota State University , Fargo , ND , USA.
authors.forename: Guilherme Volpe
authors.initials: GV
authors.lastname: Bossa
authors.affiliation: a Department of Pharmaceutical Technology , Friedrich Schiller University Jena , Jena , Germany and.
authors.forename: Christiane
authors.initials: C
authors.lastname: Decker
authors.affiliation: a Department of Pharmaceutical Technology , Friedrich Schiller University Jena , Jena , Germany and.
authors.forename: Alfred
authors.initials: A
authors.lastname: Fahr
authors.affiliation: b Department of Physics , North Dakota State University , Fargo , ND , USA.
authors.forename: Sylvio
authors.initials: S
authors.lastname: May
mesh_terms: D001798:Blood Proteins / Q000378:metabolism*; D002784:Cholesterol / Q000737:chemistry; D065546:Drug Liberation; D005227:Fatty Acids / Q000737:chemistry; D031521:Fractionation, Field Flow; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007700:Kinetics; D008055:Lipids / Q000737:chemistry; D008077:Lipoproteins, LDL / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry*; D008652:Mesoporphyrins / Q000737:chemistry* / Q000493:pharmacokinetics*; D011092:Polyethylene Glycols / Q000737:chemistry; D011485:Protein Binding
chemical_list: D001798:Blood Proteins; D005227:Fatty Acids; D008055:Lipids; D008077:Lipoproteins, LDL; D008081:Liposomes; D008652:Mesoporphyrins; D011092:Polyethylene Glycols; D002784:Cholesterol; C072269:temoporfin
keywords: AF4; modeling; pharmacokinetics; plasma proteins; temoporfin