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Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Kratzer, I; Wernig, K; Panzenboeck, U; Bernhart, E; Reicher, H; Wronski, R; Windisch, M; Hammer, A; Malle, E; Zimmer, A; Sattler, W.
Apolipoprotein A-I coating of protamine-oligonucleotide nanoparticles increases particle uptake and transcytosis in an in vitro model of the blood-brain barrier.
J Control Release. 2007; 117(3): 301-311.
Doi: 10.1016/j.jconrel.2006.11.020
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- Führende Autor*innen der Med Uni Graz
- Kratzer Ingrid
- Sattler Wolfgang
- Co-Autor*innen der Med Uni Graz
- Bernhart Eva Maria
- Hammer Astrid
- Malle Ernst
- Panzenboeck Ute
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- Abstract:
- Drug delivery to the brain is severely restricted by formation of tight junctions between adjacent brain capillary endothelial cells (BCEC). In the present study we have evaluated the effects of protamine-oligonucleotide nanoparticles (proticles) on the functional properties of primary porcine BCEC and characterized uptake and transcytosis of proticles by these cells. Proticles had no adverse effects on BCEC properties relevant to blood-brain barrier (BBB) function. Transcytosis of (125)I-labeled proticles across polarized BCEC cultures occurred in a time- and concentration-dependent manner. As apolipoproteins were suggested to enhance cellular proticle uptake, proticle coating was performed with apoA-I, the major apolipoprotein component of high density lipoproteins. Adsorption of apoA-I on the surface of proticles resulted in significantly improved uptake and transcytosis properties as compared to uncoated proticles. ApoA-I coating enhanced proticle delivery to astrocytes in an in vitro model of the BBB almost twofold. Blocking of scavenger receptor class B, type I (the prime receptor for high density lipoprotein/apoA-I that is expressed on BCEC) reduced transcytosis of apoA-I-coated proticles to levels observed for uncoated proticles. Our data indicate that apoA-I-coating of proticles could be a feasible targeting technology to improve delivery across the BBB.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Apolipoprotein A-I - pharmacology
- Astrocytes - metabolism
- Blood-Brain Barrier - drug effects
- Blotting, Western - drug effects
- Brain - cytology
- Brain Chemistry - drug effects
- Chromatography, High Pressure Liquid - drug effects
- Coculture Techniques - drug effects
- Endothelial Cells - drug effects
- Fluorescent Antibody Technique - drug effects
- Humans - drug effects
- Lipoproteins, HDL - chemistry
- Nanoparticles - chemistry
- Oligonucleotides - pharmacology
- Particle Size - pharmacology
- Protamines - pharmacology
- Spectrometry, Mass, Electrospray Ionization - pharmacology
- Swine - pharmacology
- Tetrazolium Salts - pharmacology
- Thiazoles - pharmacology
- Find related publications in this database (Keywords)
- HDL
- SR-BI
- proticles