Preparation of biodegradable cyclosporine nanoparticles by high-pressure emulsification-solvent evaporation process

摘要

The cyclic endecapeptide cyclosporine (CsA), a potent immunosuppressive drug, was incorporated into biodegradable poly (DL-lactide-co-gylcolide) (DL-PLG) 50150, 65/35 and PEG 5000-70/30 DL-PLG to improve the oral bioavailability and pharmacokinetics. Nanoparticles were prepared by a high-pressure emulsification-solvent evaporation (HPESE) process. The CsA-loaded nanoparticles were evaluated for particle size, zeta potential, surface morphology by scanning electron microscopy (SEM), thermal characterizations by differential scanning calorimetry (DSC), encapsulation efficiency (E.E.%) and in vitro release. The amount of CsA loaded into the nanoparticles was determined using high-performance liquid chromatography (HPLC) at a detection wavelength of 210 nm. The mobile phase was acetonitrile-water (70:30% v/v) and flow rate was set at 1.5 ml min(-1). The photon correlation spectroscopy showed that the particles size were < 250 nm and polydispersity index (PI) < 0.14. The zeta potential was positive for 200 mg and negative for 400 mg of polymer composition, respectively. The SEM micrographs revealed that the nanoparticles were spherical and smooth. The drug loading was between 82% and 92%. Differential scanning calorimetry (DSC) studies did not show the melting endotherm for CsA in the drug-loaded nanoparticles. In-vitro release in intestinal fluid pH 6.8 (USP XXIV) showed a cumulative percent release of 30-45% CsA in 8 h. The physicochemical properties showed that the DL-PLG and PEG-DLPLG nanoparticles could be an effective carrier for oral CsA delivery. The reported method is easy, reproducible and can be automated for batch scale production. (C) 2004 Elsevier B.V. All rights reserved.