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 extremely hydrophobic. Marketed formulations employ solubilising agents to facilitate absorption in the gastrointestinal tract. In this study, cyclosporin A nanospheres were prepared by precipitation in an aqueous surfactant solution. The particle matrix consists of the drug itself. Drug was dissolved in acetone and mixed rapidly with an aqueous solution of polysorbate 80 and sodium dodecyl sulphate (SDS). The acetone was evaporated to give a colloidal precipitate of spherical particles. Particle size could be controlled by varying the quantity of starting materials to give nanospheres of Z-average diameters in the range 250-900 nm with low polydispersity. The oral absorption of CYA from these nanospheres was compared to absorption from a microemulsion formulation in the dog. The relative bioavailability of cyclosporin 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.