In vitro cytotoxicity of liposome-encapsulated doxorubicin: dependence on liposome composition and drug release
| Autor: | Alberto Gabizon, Aviva T. Horowitz, Yechezkel Barenholz |
|---|---|
| Rok vydání: | 1992 |
| Předmět: |
Nigericin
Biophysics Ionophore Phospholipid Synthetic membrane macromolecular substances Pharmacology Biochemistry chemistry.chemical_compound Tumor Cells Cultured polycyclic compounds medicine Humans Doxorubicin Cytotoxicity Ovarian Neoplasms Liposome technology industry and agriculture Cell Biology carbohydrates (lipids) Kinetics chemistry Liposomes Drug delivery Female Cell Division medicine.drug |
| Zdroj: | Biochimica et Biophysica Acta (BBA) - Biomembranes. 1109:203-209 |
| ISSN: | 0005-2736 |
| DOI: | 10.1016/0005-2736(92)90084-y |
| Popis: | We have investigated the in vitro cytotoxicity of free doxorubicin (DOX) and liposome-entrapped DOX (L-DOX) against a human ovarian carcinoma cell line (OV-1063) using a colorimetric assay. DOX was encapsulated in the inner water phase of liposomes by an ammonium sulfate-generated proton gradient. Liposomes varied in phospholipid composition but were of a similar size. It was found that the cytotoxic activity of L-DOX is substantially decreased when liposomes containing phospholipids of high phase-transition temperature (Tm) are used. The type of negatively charged headgroup did not have any significant influence on the cytotoxicity observed. Experiments using resin beads that bind free and protein-bound DOX, but do not interact with L-DOX, indicated that the cytotoxic effect is mediated by the release of drug from the liposomes into the extracellular medium; no evidence was found for direct cellular uptake of liposome-encapsulated drug. The use of the ionophore nigericin to induce the release of DOX from high-Tm liposomes increased cytotoxicity to a level comparable to free DOX, suggesting that 'remote release' techniques may substantially improve the efficiency of liposome-mediated drug delivery and allow for the full exploitation of the favorable pharmacokinetic properties of specific high-Tm formulations. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|