title: Physicochemical characterization of stealth liposomes encapsulating an organophosphate hydrolyzing enzyme.
abstract: The present studies were focused on the preparation and characterization of stericaly stabilized liposomes (SLs) encapsulating a recombinant organophosphorus hydrolyzing phosphotriesterase (OPH) enzyme for the antagonism of organophosphorus intoxication. Earlier results indicate that the liposomal carrier system provides an enhanced protective effect against the organophosphorus molecule paraoxon, presenting a more effective therapy with less toxicity than the most commonly used antidotes. Physicochemical characterization of the liposomal OPH delivery system is essential in order to get information on its in vitro stability and in vivo fate. Osmolarity, pH, viscosity, and encapsulation efficiency of the SL preparation and the surface potential of the vesicles were determined. The membrane rigidity and the impact of OPH enzyme on it was studied by electron-paramagnetic resonance spectroscopy, using spin probes. The in vitro stability of the liposomal preparations, the vesicle size distribution, and its alteration during a 3-week storage were followed by dynamic light-scattering measurements. Further, the stability of encapsulated and nonencapsulated OPH was compared in puffer and plasma.
authors.affiliation: Department of Pharmaceutics, Semmelweis University, Budapest, Hungary. bmariann@gyok.sote.hu
authors.forename: Marianna
authors.initials: M
authors.lastname: Budai
authors.forename: Patricia
authors.initials: P
authors.lastname: Chapela
authors.forename: Pál
authors.initials: P
authors.lastname: Gróf
authors.forename: Andreas
authors.initials: A
authors.lastname: Zimmer
authors.forename: Melinda E
authors.initials: ME
authors.lastname: Wales
authors.forename: James R
authors.initials: JR
authors.lastname: Wild
authors.forename: Imre
authors.initials: I
authors.lastname: Klebovich
authors.forename: Ilona
authors.initials: I
authors.lastname: Petrikovics
authors.forename: Mária
authors.initials: M
authors.lastname: Szilasi
mesh_terms: D000931:Antidotes; D016503:Drug Delivery Systems; D006868:Hydrolysis; D008081:Liposomes / Q000737:chemistry*; D010755:Organophosphates; D010261:Paraoxon; D044345:Phosphoric Triester Hydrolases; D014783:Viscosity
chemical_list: D000931:Antidotes; D008081:Liposomes; D010755:Organophosphates; D044345:Phosphoric Triester Hydrolases; D010261:Paraoxon