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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.
Acknowledgments
The authors are grateful to Péter Kárpáti from Anton Paar Hungary Ltd. for his kind help in the viscosity measurements and to Tibor Barcza for his technical assistance. These studies were supported, in part, by research funds from the National Institutes of Health (grant no.: 5 U01 NS058035-02), the Texas Agriculture Experiment Station, and the Robert A. Welch Foundation (x-0011) at Sam Houston State University (Huntsville, Texas, USA).
Declaration of interest: The authors report no financial conflicts of interest. The authors alone are responsible for the content and writing of this paper.