Superparamagnetic iron oxide nanoparticles (SPIONs)-loaded Trojan microparticles for targeted aerosol delivery to the lung

Abstract : Targeted aerosol delivery to specific regions of the lung may improve therapeutic efficiency and minimise unwanted side effects. Targeted delivery could potentially be achieved with porous microparticles loaded with superparamagnetic iron oxide nanoparticles (SPIONs)—in combination with a target-directed magnetic gradient field. The aim of this study was to formulate and evaluate the aerodynamic properties of SPIONs-loaded Trojan microparticles after delivery from a dry powder inhaler. Microparticles made of SPIONs, PEG and hydroxypropyl-β-cyclodextrin (HPβCD) were formulated by spray drying and characterised by various physicochemical methods. Aerodynamic properties were evaluated using a next generation cascade impactor (NGI), with or without a magnet positioned at stage 2. Mixing appropriate proportions of SPIONs, PEG and HPβCD allowed Trojan microparticle to be formulated. These particles had a median geometric diameter of 2.8 ± 0.3 μm and were shown to be sensitive to the magnetic field induced by a magnet having a maximum energy product of 413.8 kJ/m3. However, these particles, characterised by a mass median aerodynamic diameter (MMAD) of 10.2 ± 2.0 μm, were considered to be not inhalable. The poor aerodynamic properties resulted from aggregation of the particles. The addition of (NH4)2CO3 and magnesium stearate (MgST) to the formulation improved the aerodynamic properties of the Trojan particles and resulted in a MMAD of 2.2 ± 0.8 μm. In the presence of a magnetic field on stage 2 of the NGI, the amount of particles deposited at this stage increased 4-fold from 4.8 ± 0.7% to 19.5 ± 3.3%. These Trojan particles appeared highly sensitive to the magnetic field and their deposition on most of the stages of the NGI was changed in the presence compared to the absence of the magnet. If loaded with a pharmaceutical active ingredient, these particles may be useful for treating localised lung disease such as cancer nodules or bacterial infectious foci.
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European Journal of Pharmaceutics and Biopharmaceutics, Elsevier, 2014, 86, pp.98 - 104. 〈10.1016/j.ejpb.2013.09.004〉
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Frederic Tewes, Carsten Ehrhardt, Anne Marie Healy. Superparamagnetic iron oxide nanoparticles (SPIONs)-loaded Trojan microparticles for targeted aerosol delivery to the lung. European Journal of Pharmaceutics and Biopharmaceutics, Elsevier, 2014, 86, pp.98 - 104. 〈10.1016/j.ejpb.2013.09.004〉. 〈inserm-01102561〉

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