| Title | Remote loading of doxorubicin into liposomes driven by a transmembrane phosphate gradient. | | Author(s) | Fritze A, Hens F, Kimpfler A, Schubert R, Peschka-Süss R | | Institution | Department of Pharmaceutical Technology and Biopharmacy, Albert-Ludwigs University, Stefan-Meier-Str. 19, 79104 Freiburg, Germany. | | Source | Biochim Biophys Acta 2006 Jun 14. | | Abstract | This study examines a new method for the remote loading of doxorubicin into liposomes. It was shown that doxorubicin can be loaded to a level of up to 98% into large unilamellar vesicles composed of egg phosphatidylcholine/cholesterol (7/3 mol/mol) with a transmembrane phosphate gradient. The different encapsulation efficiencies which were achieved with ammonium salts (citrate 100%, phosphate 98%, sulfate 95%, acetate 77%) were significantly higher as compared to the loading via sodium salts (citrate 54%, phosphate 52%, sulfate 44%, acetate 16%). Various factors, including pH-value, buffer capacity, solubility of doxorubicin in different salt solutions and base counter-flow, which likely has an influence on drug accumulation in the intraliposomal interior are taken into account. In contrast to other methods, the newly developed remote loading method exhibits a pH-dependant drug release property which may be effective in tumor tissues. At physiological pH-value doxorubicin is retained in the liposomes, whereas drug release is achieved by lowering the pH to 5.5 (approximately 25% release at 25 degrees C or 30% at 37 degrees C within two h). The DXR release of liposomes which were loaded via a sulfate gradient showed a maximum of 3% at pH 5.5. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 16887094 |
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