Elevating bioavailability of cyclosporine a via encapsulation in artificial oil bodies stabilized by caleosin.
To elevate its bioavailability via oral administration, cyclosporine A (CsA), a hydrophobic drug, was either incorporated into olive oil directly or encapsulated in artificial oil bodies (AOBs) constituted with olive oil and phospholipid in the presence or absence of recombinant caleosin purified from Escherichia coli. The bioavailabilities of CsA in these formulations were assessed in Wistar rats in comparison with the commercial formulation, Sandimmun Neoral. Among these tests, CsA-loaded AOBs stabilized by the recombinant caleosin exhibited better bioavailability than the commercial formulation and possessed the highest maximum whole blood concentration (C(max)), 1247.4 +/- 106.8 ng/mL, in the experimental animals 4.3 +/- 0.7 h (t(max)) after oral administration. C(max) and the area under the plasma concentration-time curve (AUC(0-24)) were individually increased by 50.8% and 71.3% in the rats fed with caleosin-stabilized AOBs when compared with those fed with the reference Sandimmun Neoral. The results suggest that constitution of AOBs stabilized by caleosin may be a suitable technique to encapsulate hydrophobic drugs for oral administration.
Chen
Miles C M
MC
Graduate institute of Biotechnology, National Chung-Hsing University, Taichung, Taiwan, and Department of Physiology, National Yang-Ming University, Medical College, Taipei, Taiwan.
Wang
Jui-Ling
JL
Tzen
Jason T C
JT
D000818:Animals; D001682:Biological Availability; D002135:Calcium-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000493:pharmacokinetics; D016572:Cyclosporine / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D004339:Drug Compounding; D004355:Drug Stability; D008297:Male; D000069463:Olive Oil; D010938:Plant Oils / Q000737:chemistry*; D010940:Plant Proteins / Q000737:chemistry* / Q000235:genetics / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000737:chemistry
D002135:Calcium-Binding Proteins; D000069463:Olive Oil; D010938:Plant Oils; D010940:Plant Proteins; D011994:Recombinant Proteins; C402836:caleosin protein, Sesamum indicum; D016572:Cyclosporine