Oral bioavailability of cyclosporine:: Solid lipid nanoparticles (SLN®) versus drug nanocrystals

For the development of an optimized oral formulation for cyclosporine A, 2% of this drug has been formulated in solid lipid nanoparticles (SLN (TM), mean size 157 nm) and as nanocrystals (mean size 962 nm). The encapsulation rate of SLN was found to be 96.1%. Nanocrystals are composed of 100% of drug. For the assessment of the pharmacokinetic parameters the developed formulations have been administered via oral route to three young pigs. Comparison studies with a commercial Sandimmun Neoral/Optoral (R) used as reference have been performed. The blood profiles observed after oral administration of the commercial microemulsion Sandimmun (R) revealed a fast absorption of drug leading to the observation of a plasma peak above 1000 ng/ml within the first 2 h. For drug nanocrystals most of the blood concentrations were in the range between 30 and 70 ng/ml over a period of 14 h. These values were very low, showing huge differences between the measuring time points and between the tested animals. On the contrary, administration of cyclosporine-loaded SLN led to a mean plasma profile with almost similarly low variations in comparison to the reference microemulsion, however with no initial blood peak as observed with the Sandimmun Neoral/Optoral (R). Comparing the area under the curves (AUC) obtained with the tested animals it could be stated that the SLN (TM) formulation avoids side effects by lacking blood concentrations higher than 1000 ng/ml. In this study it has been proved that using SLN (TM) as a drug carrier for oral administration of cyclosporine A a low variation in bioavailability of the drug and simultaneously avoiding the plasma peak typical of the first Sandimmune formulation can be achieved. (c) 2006 Elsevier B.V. All rights reserved.