The inhalation of medical aerosols is widely used for the treatment of lung disorders such as asthma, chronic obstructive pulmonary disease, cystic fibrosis, respiratory infection and, more recently, lung cancer. Targeted aerosol delivery to the affected lung tissue may improve therapeutic efficiency and minimize unwanted side effects. Despite enormous progress in optimizing aerosol delivery to the lung, targeted aerosol delivery to specific lung regions other than the airways or the lung periphery has not been adequately achieved to date. Here, we show theoretically by computer-aided simulation, and for the first time experimentally in mice, that targeted aerosol delivery to the lung can be achieved with aerosol droplets comprising superparamagnetic iron oxide nanoparticles--so-called nanomagnetosols--in combination with a target-directed magnetic gradient field. We suggest that nanomagnetosols may be useful for treating localized lung disease, by targeting foci of bacterial infection or tumour nodules.

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The aggregation behaviour of magnetic nanoparticles (MNP) is a decisive factor for their application in medicine and biotechnology. We extended the moment superposition model developed earlier for describing the Néel relaxation of an ensemble of immobilized particles with a given size distribution by including the Brownian relaxation mechanism. The resulting cluster moment superposition model is used to characterize the aggregation of magnetic nanoparticles in various suspensions in terms of mean cluster size, aggregate fraction, and size dispersion. We found that in stable ferrofluids 50%-80% of larger magnetic nanoparticles are organized in dimers and trimers. The scaling of the relaxation curves with respect to MNP concentration is found to be a sensitive indicator of the tendency of a MNP suspension to form large aggregates, which may limit the biocompatibility of the preparation. Scaling violation was observed in aged water based ferrofluids, and may originate from damaged MNP shells. In biological media such as foetal calf serum, bovine serum albumin, and human serum we observed an aggregation behaviour which reaches a maximum at a specific MNP concentration. We relate this to agglutination of the particles by macromolecular bridges between the nanoparticle shells. Analysis of the scaling behaviour helps to identify the bridging component of the suspension medium that causes agglutination.

Development of heparin-coated magnetic nanoparticles for targeted drug delivery applications

Due to their biocompatibility and small size, iron oxide magnetic nanoparticles (MNP) can be guided to virtually every biological environment. MNP are susceptible to external magnetic fields and can thus be used for transport of drugs and genes, for heat generation in magnetic hyperthermia or for contrast enhancement in magnetic resonance imaging of biological tissue. At the same time, their magnetic properties allow one to develop sensitive and specific measurement methods to non-invasively detect MNP, to quantify MNP distribution in tissue and to determine their binding state. In this article, we review the application of magnetorelaxometry (MRX) for MNP detection. The underlying physical properties of MNP responsible for the generation of the MRX signal with its characteristic parameters of relaxation amplitude and relaxation time are described. Existing single and multi-channel MRX devices are reviewed. Finally, we thoroughly describe some applications of MRX to cellular MNP quantification, MNP organ distribution and MNP-based binding assays. Providing specific MNP signals, a detection limit down to a few nanogram MNP, in-vivo capability in conscious animals and measurement times of a few seconds, MRX is a valuable tool to improve the application of MNP for diagnostic and therapeutic purposes.