Block-copolymer micelles as carriers of cell signaling modulators for the inhibition of JNK in human islets of Langerhans
| Autor: | Dusica Maysinger, Lawrence Rosenberg, Adi Eisenberg, Radoslav Savić, Tony Azzam, Hinyu Nedev |
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| Rok vydání: | 2009 |
| Předmět: |
endocrine system
Programmed cell death Cell signaling Materials science Polymers Blotting Western Biophysics Bioengineering In Vitro Techniques PC12 Cells Micelle Biomaterials Islets of Langerhans polycyclic compounds Animals Humans Chromatography High Pressure Liquid Micelles Anthracenes Drug Carriers geography geography.geographical_feature_category Kinase JNK Mitogen-Activated Protein Kinases respiratory system Islet Rats Cell biology Biochemistry Mechanics of Materials Cytoplasm Drug delivery Ceramics and Composites Intracellular |
| Zdroj: | Biomaterials. 30:3597-3604 |
| ISSN: | 0142-9612 |
| DOI: | 10.1016/j.biomaterials.2009.03.028 |
| Popis: | Here we investigate the potential of PCL-b-PEO micelles in preventing the cell death of isolated human islets of Langerhans. PCL-b-PEO micelles were loaded with c-Jun NH2-terminal kinases inhibitor SP600125 to rescue the isolated islets. Mechanistic studies of the uptake were conducted in PC12 cells. Incorporation of SP600125 afforded 8.2 fold greater solubility of SP600125 in micelle suspension. To investigate the effectiveness of micelle-incorporated SP600125 in preventing the islet cell death, we challenged the islets with TNF-alpha, IL-1, and IFN gamma. Micelle-incorporated SP600125 did not lose its inhibitory activity during incorporation into micelles, and it protected the islets against cytokine-induced loss of viability to the same extent as control SP600125. Moreover, the concentration of micelle-incorporated SP600125 used was 13-fold lower, demonstrating the greater efficacy of micelle delivered SP600125. Micelles maintained their cytoplasmic distribution without detectable nuclear localization in islets. The inhibition of JNK was confirmed by western blots. This study suggests that micelle-based intracellular delivery of potent, poorly water soluble, cell-death-pathway inhibitors may represent a valuable addition to established delivery of cytocidal block-copolymer micelle-incorporated bioactives. |
| Databáze: | OpenAIRE |
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