title: In vitro tests to predict in vivo performance of liposomal dosage forms.
abstract: Design of liposome-based formulations for clinical use can be assisted by employing in vitro assays to predict pharmacokinetics and bioavailability of the drug before employing costly and time-consuming in vivo studies. For such formulations of the anti-cancer drug doxorubicin (DXR) we developed two assays. (A) An assay which determines the dilution-induced DXR release in buffers and plasma. This assay was employed to evaluate two liposomal DXR formulations: (i) membrane-associated liposomal doxorubicin (L-DXR), and (ii) sterically-stabilized liposomes which encapsulate DXR in the aqueous phase of the liposomes (S-DXR). The agreement between the dilution-induced release assay in vitro and the pharmacokinetics of DXR administrated either as L-DXR or as S-DXR in humans suggests that the dilution release assay can be used as a predictor for the pharmacokinetic performance of liposomal formulations. (B) An assay which determines intracellular drug release induced by liposome degradation in the presence of mouse liver lysosome lysate. This assay was used to assess bioavailability of DXR when delivered via L-DXR, which are taken up by the reticuloendothelial system (RES). (C) An assay which complements conventional chromatographic analyses (HPLC or TLC) of the drug, in which a DXR adduct or aggregate was determined by using Sephadex LH-20 gel exclusion chromatography.
authors.affiliation: Department of Biochemistry, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
authors.forename: S
authors.initials: S
authors.lastname: Amselem
authors.forename: R
authors.initials: R
authors.lastname: Cohen
authors.forename: Y
authors.initials: Y
authors.lastname: Barenholz
mesh_terms: D000818:Animals; D001682:Biological Availability; D004317:Doxorubicin / Q000008:administration & dosage* / Q000378:metabolism / Q000493:pharmacokinetics; D004337:Drug Carriers; D004353:Drug Evaluation, Preclinical / Q000379:methods; D006801:Humans; D008081:Liposomes; D008099:Liver / Q000378:metabolism*; D008247:Lysosomes / Q000378:metabolism*; D004364:Pharmaceutical Preparations / Q000008:administration & dosage* / Q000378:metabolism; D051381:Rats
chemical_list: D004337:Drug Carriers; D008081:Liposomes; D004364:Pharmaceutical Preparations; D004317:Doxorubicin