Abstract
Multifunctional magnetoliposomes (MLs) with active and magnetic targeting potential are evaluated as platform systems for drug targeting applications. USPIO-encapsulating MLs are prepared by freeze drying/extrusion, decorated with one or two ligands for brain or cancer targeting (t-MLs), and actively loaded with Doxorubicin (DOX). MLs have mean diameters between 117 and 171 nm. Ligand attachment yields and DOX-loading efficiency are sufficiently high, 78–95% and 89–92%, respectively, while DOX loading and retention is not affected by co-entrapment of USPIOs, and USPIO loading/retention is not modulated by DOX. Attachment of ligands, also does not affect DOX or USPIO loading. Interestingly, MLs have high magnetophoretic mobility (MM) compared to free USPIOs, which is not affected by surface coating with PEG (up to 8 mol%), but is slightly reduced by Chol incorporation in their membrane, or when functional groups are immobilized on their surface. ML size, (directly related to number of USPIOs entrapped per vesicle), is the most important MM-determining factor. MM increases by 570% when ML size increases from 69 to 348 nm. Targeting potential of t-MLs is verified by enhanced: (i) transport across a cellular model of the blood-brain-barrier, and (ii) anti-proliferative effect towards B16 melanoma cells. The potential of further enhancing t-ML targeting magnetically is verified by additional enhancements of (i) and (ii), when experiments are performed under a permanent magnetic field.
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