title: Comparative permeability and diffusion kinetics of cyclosporine A liposomes and propylene glycol solution from human lung tissue into human blood ex vivo.
abstract: Aerolized cyclosporine A (CsA) has been successfully used for prevention of organ rejection in lung transplant recipients. Various formulations of CsA are available and so far no direct comparison of their pharmacokinetics has been performed. Since clinical studies are elaborate, we sought a way to predict the kinetic behaviour of a propylene glycol solution of CsA (CsA-PG) and a liposomal formulation (L-CsA). The permeability across the human bronchial cell line Calu-3 revealed low permeability for CsA with the apparent permeability for CsA-PG being twice as high as for L-CsA. Employing a previously described dialysis model, the diffusion of CsA from human lung tissue into human blood was determined ex vivo. Consistent with the cell culture model results, we observed that the degree and rate of drug transfer into human blood was more pronounced for CsA-PG than for L-CsA with the area under the curve (AUC) of CsA-PG being about 1.6 times higher than for the L-CsA formulation. The diffusion rate was more than 50% higher from CsA-PG than from the liposomes. To conclude, both model systems consistently revealed that L-CsA displayed clearly a prolonged release effect and favourable longer tissue retention than CsA-PG.
authors.affiliation: Universität Würzburg, Würzburg, Germany.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Trammer
authors.forename: Annette
authors.initials: A
authors.lastname: Amann
authors.forename: Eleonore
authors.initials: E
authors.lastname: Haltner-Ukomadu
authors.forename: Sascha
authors.initials: S
authors.lastname: Tillmanns
authors.forename: Manfred
authors.initials: M
authors.lastname: Keller
authors.forename: Petra
authors.initials: P
authors.lastname: Högger
mesh_terms: D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical; D016572:Cyclosporine / Q000097:blood / Q000737:chemistry / Q000378:metabolism*; D003956:Dialysis; D004058:Diffusion; D004339:Drug Compounding; D017097:Electric Impedance; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood / Q000737:chemistry / Q000378:metabolism*; D007700:Kinetics; D008081:Liposomes; D008168:Lung / Q000378:metabolism*; D010539:Permeability; D019999:Pharmaceutical Solutions; D010713:Phosphatidylcholines / Q000737:chemistry*; D019946:Propylene Glycol / Q000737:chemistry*
chemical_list: D007166:Immunosuppressive Agents; D008081:Liposomes; D019999:Pharmaceutical Solutions; D010713:Phosphatidylcholines; D019946:Propylene Glycol; D016572:Cyclosporine