title: Polymeric nanocapsules with SEDDS oil-core for the controlled and enhanced oral absorption of cyclosporine.
abstract: 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(0-24h) 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.
authors.affiliation: Department of Drug Development and UNIDDS, School of Medicine, Inha University, 8F A-dong, Jeongseok Bldg., Sinheung-dong 3-ga, Jung-gu, Incheon 400-712, South Korea.
authors.forename: Min-Jeong
authors.initials: MJ
authors.lastname: Park
authors.forename: Prabagar
authors.initials: P
authors.lastname: Balakrishnan
authors.forename: Su-Geun
authors.initials: SG
authors.lastname: Yang
mesh_terms: D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D016572:Cyclosporine / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D003692:Delayed-Action Preparations; D004058:Diffusion; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D004655:Emulsions; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D053769:Nanocapsules; D009821:Oils / Q000737:chemistry; D010316:Particle Size; D010539:Permeability; D011091:Polyesters / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D012997:Solvents / Q000737:chemistry
chemical_list: D003692:Delayed-Action Preparations; D004337:Drug Carriers; D004655:Emulsions; D007166:Immunosuppressive Agents; D053769:Nanocapsules; D009821:Oils; D011091:Polyesters; D012997:Solvents; C033616:poly(lactide); D016572:Cyclosporine