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Combined magnetoliposome formation and drug loading in one step for efficient AC-magnetic Field Remote Controlled Drug Release

AuthorsFortes Brollo, María Eugenia; Domínguez-Bajo, Ana; Tabero, Andrea; Domínguez-Arca, Vicente; García-Gisbert, Víctor; Prieto, Gerardo; Johansson, Christer; García García, Ricardo CSIC ORCID ; Villanueva, Angeles; Serrano, María C. CSIC ORCID; Morales, M. P. CSIC ORCID
KeywordsSuperparamagnetic iron oxide nanoparticle
Drug delivery carrier
MDA-MB-231 cells
HeLa cells
Magnetic hyperthermia
Issue Date6-Jan-2020
PublisherAmerican Chemical Society
CitationACS Applied Materials and Interfaces
Abstract[EN] We have developed a reproducible and facile one step strategy for the synthesis of doxorubicin loaded magnetoliposomes by using a thin-layer evaporation method. Liposomes of around 200 nm were made of 1,2-Dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and iron oxide nanoparticles (NP) with negative, positive and hydrophobic surfaces that were incorporated outside, inside or between the lipid bilayers, respectively. To characterize how NP are incorporated in liposomes, advanced cryoTEM and atomic force microscope (AFM) techniques have been used. It was observed that only when the NP are attached outside the liposomes, the membrane integrity is preserved (lipid melt transition shifts to 38.7 ºC with high enthalpy 34.8 J/g) avoiding the leakage of encapsulated drug while having good colloidal properties and the best heating efficiency under an alternating magnetic field (AMF). These magnetoliposomes were tested with two cancer cell lines, MDA-MB-231 and HeLa cells. First, 100 % of cellular uptake was achieved with a high cell survival (above 80 %), which is preserved for doxorubicin loaded magnetoliposomes (83 %). Then, we demonstrate that doxorubicin release can be triggered by remote control using a non-invasive external AMF for 1 hour, leading to a cell survival reduction of 20 %. Magnetic field conditions of 202 kHz and 30 mT seem to be enough to produce an effective heating avoiding drug degradation. In conclusion, these drug loaded magnetoliposomes prepared in one step could be used for an efficient drug release on demand at a specific time and place using an external AMF and reducing or even eliminating side effects.
Publisher version (URL)https://doi.org/10.1021/acsami.9b20603
Appears in Collections:(ICMM) Artículos
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