Physicochemical characterization of stealth liposomes encapsulating an organophosphate hydrolyzing enzyme.
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.
Budai
Marianna
M
Department of Pharmaceutics, Semmelweis University, Budapest, Hungary. bmariann@gyok.sote.hu
Chapela
Patricia
P
Gróf
Pál
P
Zimmer
Andreas
A
Wales
Melinda E
ME
Wild
James R
JR
Klebovich
Imre
I
Petrikovics
Ilona
I
Szilasi
Mária
M
D000931:Antidotes; D016503:Drug Delivery Systems; D006868:Hydrolysis; D008081:Liposomes / Q000737:chemistry*; D010755:Organophosphates; D010261:Paraoxon; D044345:Phosphoric Triester Hydrolases; D014783:Viscosity
D000931:Antidotes; D008081:Liposomes; D010755:Organophosphates; D044345:Phosphoric Triester Hydrolases; D010261:Paraoxon