Nanospheres of cyclosporin A: poor oral absorption in dogs

The cyclic undecapeptide cyclosporin A (CYA) used as first-line therapy in the prevention of xenograft rejection following organ transplantation, is e xtremely hydrophobic. Marketed formulations employ solubilising agents to f acilitate absorption in the gastrointestinal tract. In this study, cyclospo rin A nanospheres were prepared by precipitation in an aqueous surfactant s olution. The particle matrix consists of the drug itself. Drug was dissolve d in acetone and mixed rapidly with an aqueous solution of polysorbate 80 a nd sodium dodecyl sulphate (SDS). The acetone was evaporated to give a coll oidal precipitate of spherical particles. Particle size could be controlled by varying the quantity of starting materials to give nanospheres of Z-ave rage diameters in the range 250-900 nm with low polydispersity. The oral ab sorption of CYA from these nanospheres was compared to absorption from a mi croemulsion formulation in the dog. The relative bioavailability of cyclosp orin A from nanospheres was only 3%, based on comparison of the area under the blood concentration-time curve (AUC) values for the two formulations. ( C) 1999 Elsevier Science B.V. All rights reserved.