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Cochleate formulations of Amphotericin b designed for oral administration using a naturally occurring phospholipid
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International audience. Co chleates Am photeri cin B Or al bioa va il ab il ity Ca co2 cell s sy nchro tron SA XS Ci rcula r dichro is m ABSTRACT The pu rpose of this work is to formu late the poor soluble antifungal and antiparasitic agent Am ph otericin B (AmB) in cost-effective lipid-based formu lations suitable for oral use in developing coun tries, overcoming the limitations of poor water solubility, neph rotoxicity and low oral bioavailability. The antifungal agent was formu lated, at different molar proportions, in coch leate nanocarriers prepared using an accessible naturally occu rring ph osph olipid rich in ph osph atidylserine (Lipoid PSP7 0). These nanoassemblies were prepared by condensation of negatively ch arged ph osph olipid me mbrane vesicles with divalent cations (Ca 2+). Small-angle X-ray scattering stud ies revealed the Ca 2+-triggered condensation of loosely packed mu ltilam ellar vesicles into tightly packed bilayers of strongly dehydrated mu ltilam ellar organization ch aracterized by narrow Bragg peaks. Transmission electron microscopy and quasi-elastic light scattering studies demonstrated the forma tion of nanosized particles. Am B drug loading was above 55 % in all formu lations. Circu lar dich roism demonstrated the prevalenc e of monome ric and complexed form s of Am B over toxic aggregates. The stability of Am B in gastric me dium was improved by loading in coch leates and its release in gastrointestinal me dia was retarded. Confocal microscopy stud ies revealed the in-vi tro interactions of Lipoid PSP7 0-based coch leates with Caco2 intestinal cell monolayers. The results suggest that the lowcost Am B-loaded coch leates ma y increase the therapeutic range of this drug.
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