Preparation of an alternative freeze-dried pH-sensitive cyclosporine A loaded nanoparticle formulation and its pharmacokinetic profile in rats

This work aimed to produce and develop new pH-sensitive cyclosporine A (CyA) loaded nanoparticles (CyA-NP) based on the enterically soluble copolymer Eudragit® S100 and to improve the poor bioavailability of lipophilic CyA. CyA-NP and freeze-dried nanoparticles (Lac-CyA-NP, 3% lactose as cryoprotectant) were prepared using a quasi-emulsion solvent diffusion technique and freeze-drying. The encapsulation efficiency, particle size and in vitro release characteristics from the vehicle of CyA were studied individually. The bioavailability of CyA-NP and Lac-CyA-NP was evaluated in rats at a dose of 15 mg/kg as compared to Neoral®. The mean particle size of CyA-NP was 44 ± 3 nm, while the encapsulation efficiency reached 99.7%. The particle size and encapsulation efficiency of the freeze-dried formulation remained relatively stable by using 3% lactose (W/V) as a cryoprotective agent before freeze-drying and after dissolving. Significantly pH-dependent release profiles were revealed when the pH of the medium was above 6.0. The relative bioavailabilities of CyA-NP and Lac-CyA-NP were 162.1% and 130.1% compared with Neoral® after oral administration at the same dosage. The results showed that the pH-sensitive CyA-loaded nanoparticles were a potential vehicle for developing a high performance CyA carrier system.