Polymeric nanocapsules with SEDDS oil-core for the controlled and enhanced oral absorption of cyclosporine

Self-microemulsifying drug delivery system (SEDDS) cored-polymeric nanocapsules (NC) were fabricated using emulsion diffusion method for the controlled oral absorption of the poorly water soluble drug, cyclosporine. Poly-dl-lactide (PDLLA) was used as the shell-forming polymer. The NCs in different polymer/oil ratios (from 25/125 to 125/125) were prepared following a solvent-diffusion method. Especially, the SEDDS oil-core compositions, which can form microemulsions on dispersion, were selected based on a pseudo-phase diagram study and further optimized based on the solubility and permeability studies. The prepared NCs were with a mean diameter of 150-220 nm and 9.4-4.5% w/w drug loading. In vivo study in rats showed that the optimized NC(50/125) and NC(100/125) released the drug in controlled way as well as enhanced the bioavailability significantly with AUC(0-24 h) values of 14880.3 +/- 1470.6 and 12657.8 +/- 754.5 ng h/ml, respectively, compared to that of SEDDS-core solution (9878.9 +/- 409.6 ng h/ml). Moreover it was observed that the NCs maintained blood concentration of cyclosporine (> 500 ng/ml) for 14-20 h but in the case of control formulation it was only 7.33 h. Our results suggest that the prepared NCs could be a potential carrier for the oral controlled release formulation of cyclosporine. (C) 2012 Elsevier B.V. All rights reserved.