In this paper we describe the effect of a low frequency alternating magnetic field (LF-AMF) on the structure and permeability of magnetoliposomes, i.e. liposomes formulated in the presence of magnetic nanoparticles. Hydrophobic cobalt ferrite nanoparticles (CoFe(2)O(4)) coated with a shell of oleic acid were prepared, characterized and employed in the preparation of magnetoliposomes. The stability of the lipid bilayer after the application of an oscillating magnetic field was studied by means of Dynamic Light Scattering (DLS), Small Angle Scattering of X-rays (SAXS) and Differential Scanning Calorimetry (DSC). The enhancement of liposome permeability upon LF-AMF exposure was measured as the self-quenching decrease of the fluorescent molecule carboxyfluorescein (CF) entrapped in the liposome pool. Carboxyfluorescein leakage from magnetoliposomes was investigated as a function of field frequency, time of exposure to the magnetic field, and cobalt ferrite nanoparticles concentration. Kinetics of CF release from LF-AMF treated magnetoliposomes, monitored through the fluorescence intensity increase during time, highlights a slow release of CF during the first hours, followed by a faster release a few hours after the field treatment which leads to a complete leakage of CF. DSC provides insights about the effect of the LF-AMF treatment, showing that the first few hours correspond to a complete loss of the transition peak from the lamellar gel (L beta) phase to the liquid crystalline (L alpha) phase of the PC bilayers. These results suggest that the slow release takes place through the formation of local pores or defects at the membrane level, while the fast release corresponds to an increased permeability of the membrane that can be related to a structural change of the bilayer.
"The tested models are: Higuchi , Korsmeyer-Peppas     , and Weibull  . These models share a similar mathematical form: (i) the released amount of drug is described as the ratio between the cumulative amount of drug released at time t, M t , and infinite time, M ∞ ; (ii) time is scaled by a factor k; (iii) dependency on time is defined according to a power law. "
"A loss of membrane structure and an increase in permeability is observed if the nanoparticle shell is not irreversibly linked to the core. For example, nonleaking liposomes were observed for nanoparticles stabilized with palmityl-nitroDOPA , while liposomes containing oleic acid stabilized nanoparticles in the membrane showed membrane deformation and rapid passive leaking   . The much higher stability of the nitro- DOPA-anchored compared to carboxyl-anchored dispersants  made it possible to control cargo release by pulsing the applied AMF . "
[Show abstract][Hide abstract] ABSTRACT: Superparamagnetic iron oxide nanoparticles are used in a rapidly expanding number of research and practical applications in biotechnology and biomedicine. We highlight how recent developments in iron oxide nanoparticle design and understanding of nanoparticle membrane interactions have led to applications in magnetically triggered, liposome delivery vehicles with controlled structure. Nanoscale vesicles actuated by incorporated nanoparticles allow for controlling location and timing of compound release, which enables e.g. use of more potent drugs in drug delivery as the interaction with the right target is ensured. This review emphasizes recent results on the connection between nanoparticle design, vesicle assembly and the stability and release properties of the vesicles. While focused on lipid vesicles magnetically actuated through iron oxide nanoparticles, these insights are of general interest for the design of capsule and cell delivery systems for biotechnology controlled by nanoparticles.
New Biotechnology 12/2014; 32(6). DOI:10.1016/j.nbt.2014.12.002 · 2.90 Impact Factor
"Magnetoliposomes, which are formed by encapsulating iron oxide nanoparticles within liposomes, have attracted interest as controlled release drug delivery agents due to their ability to change structure and permeability under low frequency magnetic fields    . A new method of magnetoliposome formation was introduced by Chen et al. "
[Show abstract][Hide abstract] ABSTRACT: Low-dose (LD) chemotherapy is a promising treatment strategy that may be improved by controlled delivery. Polyethylene glycol-stabilized bilayer-decorated magnetoliposomes (dMLs) have been designed as a stimuli-responsive LD chemotherapy drug delivery system and tested in vitro using Huh-7 hepatocellular carcinoma cell line. The dMLs contained hydrophobic superparamagnetic iron oxide nanoparticles within the lipid bilayer and doxorubicin hydrochloride (DOX, 2μM) within the aqueous core. Structural analysis by cryogenic transmission electron microscopy and dynamic light scattering showed that the assemblies were approximately 120nm in diameter. Furthermore, the samples consisted of a mixture of dMLs and bare liposomes (no nanoparticles), which provided dual burst and spontaneous DOX release profiles, respectively. Cell viability results show that the cytotoxicity of DOX-loaded dMLs was similar to that of bare dMLs (∼10%), which indicates that spontaneous DOX leakage had little cytotoxic effect. However, when subjected to a physiologically acceptable radiofrequency (RF) electromagnetic field, cell viability was reduced up to 40% after 8h and significant cell death (>90%) was observed after 24h. The therapeutic mechanism was intracellular RF-triggered DOX release from the dMLs and not intracellular hyperthermia due to nanoparticle heating via magnetic losses.
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