skip to content
Dovepress - Open Access to Scientific and Medical Research
View our mobile site

8129

Pharmacokinetics and enhanced oral bioavailability in beagle dogs of cyclosporine A encapsulated in glyceryl monooleate/poloxamer 407 cubic nanoparticles

Original Research

(2478) Views  (965) Full article downloads

Authors: Jie Lai, Yi Lu, Zongning Yin, et al

Published Date December 2009 Volume 2010:5 Pages 13 - 23
DOI: http://dx.doi.org/10.2147/IJN.S8311

Jie Lai1,2, Yi Lu1, Zongning Yin2, Fuqiang Hu3, Wei Wu1

1School of Pharmacy, Fudan University, Shanghai, China, 2West China School of Pharmacy, Sichuan University, Chengdu, China, 3School of Pharmacy, Zhejiang University, Hangzhou, China

Abstract: Efforts to improve the oral bioavailability of cyclosporine A (CyA) remains a challenge in the field of drug delivery. In this study, glyceryl monooleate (GMO)/poloxamer 407 cubic nanoparticles were evaluated as potential vehicles to improve the oral bioavailability of CyA. Cubic nanoparticles were prepared via the fragmentation of a bulk GMO/poloxamer 407 cubic phase gel by sonication and homogenization. The cubic inner structure formed was verified using Cryo-TEM. The mean diameters of the nanoparticles were about 180 nm, and the entrapment efficiency of these particles for CyA was over 85%. The in vitro release of CyA from these nanoparticles was less than 5% at 12 h. The results of a pharmacokinetic study in beagle dogs showed improved absorption of CyA from cubic nanoparticles as compared to microemulsion-based Neoral®; higher Cmax (1371.18 ± 37.34 vs 969.68 ± 176.3 ng mL-1), higher AUC0–t (7757.21 ± 1093.64 vs 4739.52 ± 806.30 ng h mL-1) and AUC0–∞ (9004.77 ± 1090.38 vs 5462.31 ± 930.76 ng h mL-1). The relative oral bioavailability of CyA cubic nanoparticles calculated on the basis of AUC0–∞ was about 178% as compared to Neoral®. The enhanced bioavailability of CyA is likely due to facilitated absorption by cubic nanoparticles rather than improved release.

Keywords: nanoparticles, cubosomes, cyclosporine A, glyceryl monooleate, oral drug delivery, bioavailability, beagle dogs






 

Other articles by Professor Wei Wu

Enhanced oral bioavailability of cyclosporine A by liposomes containing a bile salt
Food protein-stabilized nanoemulsions as potential delivery systems for poorly water-soluble drugs: preparation, in vitro characterization, and pharmacokinetics in rats
Liposomes containing glycocholate as potential oral insulin delivery systems: preparation, in vitro characterization, and improved protection against enzymatic degradation
Solid self-nanoemulsifying cyclosporin A pellets prepared by fluid-bed coating: preparation, characterization and in vitro redispersibility