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Journal of Drug Delivery
Volume 2012, Article ID 626417, 8 pages
Research Article

Native and Complexed IGF-1: Biodistribution and Pharmacokinetics in Infantile Neuronal Ceroid Lipofuscinosis

1A.I. Virtanen Institute, University of Eastern Finland, 70211 Kuopio, Finland
2Biocenter Kuopio, University of Eastern Finland, 70211 Kuopio, Finland
3School of Pharmacy, University of Eastern Finland, 70211 Kuopio, Finland
4National Institute for Health and Welfare, Public Health Genomics Unit, Biomedicum Helsinki, Haartmaninkatu 8, 00290 Helsinki, Finland
5Department of Physics and Astronomy, University of Turku, 20014 Turku, Finland
6Department of Pediatrics, Kuopio University Hospital, 70211 Kuopio, Finland

Received 22 February 2012; Revised 11 April 2012; Accepted 18 April 2012

Academic Editor: Jia You Fang

Copyright © 2012 Tuulia Huhtala et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Infantile neuronal ceroid lipofuscinosis (INCL) is a severe neurodegenerative disorder of childhood characterized by selective death of cortical neurons. Insulin-like growth factor 1 (IGF-1) is important in embryonic development and is considered as a potential therapeutic agent for several disorders of peripheral and central nervous systems. In circulation IGF-1 is mainly bound to its carrier protein IGFBP-3. As a therapeutic agent IGF-1 has shown to be more active as free than complexed form. However, this may cause side effects during the prolonged treatment. In addition to IGFBP-3 the bioavailability of IGF-1 can be modulated by using mesoporous silicon nanoparticles (NPs) which are optimal carriers for sustained release of unstable peptide hormones like IGF-1. In this study we compared biodistribution, pharmacokinetics, and bioavailability of radiolabeled free IGF-1, IGF-1/IGFBP-3, and IGF-1/NP complexes in a Cln1-/- knockout mouse model. IGF-1/NP was mainly accumulated in liver and spleen in all studied time points, whereas minor and more constant amounts were measured in other organs compared to free IGF-1 or IGF-1/IGFBP-3. Also concentration of IGF-1/NP in blood was relatively high and stable during studied time points suggesting continuous release of IGF-1 from the particles.