The encapsulation of idarubicin within liposomes using the novel EDTA ion gradient method ensures improved drug retention in vitro and in vivo

The application of EDTA in drug delivery systems: doxorubicin liposomes loaded via NH4EDTA gradient

“…34 A similar result was obtained in liposomes loaded with idarubicin by an NH 4 EDTA gradient. 31 In the current solubility studies, the biggest difference in DOX solubility between NH 4 EDTA and (NH 4 ) 2 SO 4 solutions appeared at pH 4. The solubility of DOX seemed ten times greater in the NH 4 EDTA solution than in the (NH 4 ) 2 SO 4 solution.…”

“…[34][35][36] If the loaded drug forms an insoluble complex with the hydration medium in the liposomes, and the dissolution rate of the complex is slower than that of the drug departing through the bilayer, then increased drug retention will be observed. 31 In addition to drug properties, retention is also dependent on the anionic varieties present and concentrations of the inner aqueous medium. When citric acid and ammonium sulfate gradients were employed to load DOX into liposomes, precipitation was observed as fiber bundles by cryo-electron microscopy with no observable membrane invagination.…”

“…13 Previous studies have shown that liposomes prepared by a transmembrane NH 4 EDTA gradient method can significantly increase drug retention and decrease liposome-related damage to the immune system compared with liposomes prepared by other gradient methods. 31,32 Finally, EDTA binds to calcium, which should lead to a decreased incidence rate of hypercalcinemia and improve the quality of life of advanced cancer patients. 16 In this paper, EDTA was used in a drug delivery system to encapsulate doxorubicin into liposomes using a transmembrane NH 4 EDTA gradient.…”

Cyclodextrin-based star polymers as a versatile platform for nanochemotherapeutics: Enhanced entrapment and uptake of idarubicin

“…IDA is reported to be 5-10 times more potent but less cardiotoxic than daunorubicin. Both IDA and its lipophilic metabolite daunorubicinole are considered unique BBB-crossing anthracyclines [20]. However, IDA shares the same side effects associated with other anthracyclines including multiple drug resistance, secondary acute myelogenous leukemia, cardiotoxicity and neutropenia.…”

“…Promising approaches to encapsulate IDA in nanocarriers for better therapeutic efficacy and lower toxicological effects include IDA liposomal formulations. Unfortunately, unlike liposomal doxorubicin (Doxil ® ) and daunorubicin (DaunoXome ® ), IDA was found to rapidly leak from cholesterol-containing liposomes into the blood stream [20][21][22]. Leakage can be attributed to cholesterol-IDA interactions enforced by the presence of negatively charged lipids, leading to drug transport across the bilayer.…”