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. 2012:2012:626417.
doi: 10.1155/2012/626417. Epub 2012 Jun 15.

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

Tuulia Huhtala  1 , Jussi Rytkönen, Anu Jalanko, Martti Kaasalainen, Jarno Salonen, Raili Riikonen, Ale Närvänen
Affiliations

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

Tuulia Huhtala et al. J Drug Deliv. 2012.

Abstract

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.

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Figures

Figure 1
Figure 1
In vitro release of 125-I labelled IGF-1 from nanoparticles. 20% of the IGF-1 was burst immediately after mixing with mouse plasma and 50% was released after 20 minutes incubation at 37°C. Only 15% was released between 20 and 240 min time points.
Figure 2
Figure 2
(a) Clearance of unbound and complexed IGF-1 in vivo. (b) Pharmacokinetics of free and complexed IGF-1 in selected organs.
See this image and copyright information in PMC

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References

    1. Santavuori P. Neuronal ceroid-lipofuscinoses in childhood. Brain and Development. 1988;10(2):80–83. - PubMed
    1. Vesa J, Hellsten E, Verkruyse LA, et al. Mutations in the palmitoyl protein thioesterase gene causing infantile neuronal ceroid lipofuscinosis. Nature. 1995;376(6541):584–587. - PubMed
    1. Riikonen R, Vanhanen SL, Tyynelä J, Santavuori P, Turpeinen U. CSF insulin-like growth factor-1 in infantile neuronal ceroid lipofuscinosis. Neurology. 2000;54(9):1828–1832. - PubMed
    1. Jalanko A, Vesa J, Manninen T, et al. Mice with Ppt1 Δex4 mutation replicate the INCL phenotype and show an inflammation-associated loss of interneurons. Neurobiology of Disease. 2005;18(1):226–241. - PubMed
    1. Macauley SL, Wozniak DF, Kielar C, Tan Y, Cooper JD, Sands MS. Cerebellar pathology and motor deficits in the palmitoyl protein thioesterase 1-deficient mouse. Experimental Neurology. 2009;217(1):124–135. - PMC - PubMed