Preparation of an alternative freeze-dried pH-sensitive cyclosporine A loaded nanoparticles 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.
Yang
Zhi-Qiang
ZQ
College of Pharmacy, Soochow University, Jiangsu, Suzhou, China.
Xu
Jie
J
Pan
Ping
P
Zhang
Xue-Nong
XN
D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D003451:Cryoprotective Agents / Q000737:chemistry; D016572:Cyclosporine / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D004339:Drug Compounding; D005612:Freeze Drying; D006863:Hydrogen-Ion Concentration; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D008297:Male; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles; D010316:Particle Size; D051381:Rats; D017207:Rats, Sprague-Dawley
D003451:Cryoprotective Agents; D007166:Immunosuppressive Agents; D016572:Cyclosporine