Magnetic alginate microspheres: system for the position controlled delivery of nerve growth factor
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The use of polymeric carriers containing dispersed magnetic nanocrystalline particles for targeted delivery of drugs in clinical practice has attracted the interest of the scientific community. In this paper a system comprised of alginate microparticles with a core of magnetite and carrying nerve growth factor (NGF) is described. The magnetic properties of these microspheres, typical of superparamagnetic materials, allow precise and controlled delivery to the intended tissue environment. Experiments carried out on PC12 cells with magnetic alginate microspheres loaded with NGF have confirmed the induction of cell differentiation which is strongly dependent on the distance from the microsphere cluster. In addition, finite element modelling (FEM) of the release profile from the microspheres in culture, indicated the possibility of creating defined and predictable NGF gradients from the loaded microspheres. These observations on the carriage and release of growth factors by the proposed microparticles open new therapeutic options for both neuronal regeneration and of the development of effective neuronal interfaces.
KeywordsTargeted drug delivery NGF Alginate Magnetic microparticles Neuronal outgrowth
The work described in this paper was partially supported by the IIT (Italian Institute of Technology) Network and the NINIVE (Non Invasive Nanotransducer for In Vivo gene thErapy, STRP 033378) project, co-financed by the 6FP of the European Commission.
Authors gratefully thank Mr. Carlo Filippeschi for his kind support using the FIB microscope.
- L.A. Greene, S.E. Farinelli, M.E. Cunningham, D.S. Park, in Culture and experimental use of the PC12 rat pheochromocytoma cell line, in: Culturing Nerve Cells 2, ed. by F. Banker, K. Goslin (MIT Press, Cambridge, 1998)Google Scholar
- B.P. Hanley, L. Xing, R.H. Cheng, Variance in multiplex suspension array assays: microsphere size variation impact. Theoretical Biology and Medical Modelling 4(31), 8 (2007)Google Scholar
- R. Heumann, D. Lindholm, C. Bandtlow, M. Meyer, M.J. Radeke, T.P. Misko, E. Shooter, H. Thoenen, Differential regulation of mRNA encoding nerve growth factor and its receptor in rat sciatic nerve during development, degeneration, and regeneration: role of macrophages. Proc. Natl. Acad. Sci. USA 84, 8735–8739 (1987)CrossRefGoogle Scholar
- R. Langer, Drug delivery and targeting. Nature 392, 5–10 (1998)Google Scholar
- X. Navarro, S. Calvet, C.A. Rodriguez, C. Blau, M. Buti, E. Valderrama, J.U. Meyer, T. Stieglitz, Stimulation and recording from regenerated peripheral nerves through polyimide sieve electrodes. J. Periph. Nerv. System 3, 91–101 (1998)Google Scholar
- V. Raffa, P. Castrataro, A. Menciassi, P. Dario, in In Applied scanning probe methods, vol. II, ed. by B. Bushan, H. Fuchs (Springer, Heidelberg, 2005)Google Scholar
- P. Sapra, T.M. Allen, Internalizing antibodies are necessary for improved therapeutic efficacy of antibody-targeted liposomal drugs. Cancer Res. 62(24), 7190–7194 (2002)Google Scholar
- K.J. Widder, A.E. Senyei, D.G. Scarpelli, Magnetic microspheres: a model system for site specific drug delivery in vivo. Proc. Soc. Exp. Biol. Med. 158(2), 141–146 (1978)Google Scholar
- U. Zimmermann, G. Pilwat, Organ specific application of drugs by means of cellular capsule systems. J. Biosci. 31(11–12), 732–736 (1976)Google Scholar