Choline Derivate-Modified Doxorubicin Loaded Micelle for Glioma Therapy
| Autor: | Huiying Yang, Yubo Guo, Haojun Ma, Chen Jiang, Yujie Zhang, Xutao Jiang, Xi He, Jianfeng Li, Sai An |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Biodistribution
Materials science Proton Magnetic Resonance Spectroscopy Cmax Antineoplastic Agents macromolecular substances Polyethylene glycol Micelle Choline Polyethylene Glycols Rats Sprague-Dawley Mice chemistry.chemical_compound Pharmacokinetics PEG ratio medicine Animals Humans Tissue Distribution General Materials Science Doxorubicin Micelles Brain Neoplasms technology industry and agriculture Glioma Flow Cytometry Biochemistry chemistry Drug delivery Subcellular Fractions medicine.drug Nuclear chemistry |
| Zdroj: | ACS Applied Materials & Interfaces. 7:21589-21601 |
| ISSN: | 1944-8252 1944-8244 |
| Popis: | Ligand-mediated polymeric micelles have enormous potential for improving the efficacy of glioma therapy. Linear-dendritic drug-polymer conjugates composed of doxorubicin (DOX) and polyethylene glycol (PEG) were synthesized with or without modification of choline derivate (CD). The resulting MeO-PEG-DOX8 and CD-PEG-DOX8 could self-assemble into polymeric micelles with a nanosized diameter around 30 nm and a high drug loading content up to 40.6 and 32.3%, respectively. The optimized formulation 20% CD-PEG-DOX8 micelles had superior cellular uptake and antitumor activity against MeO-PEG-DOX8 micelles. The subcellular distribution using confocal study revealed that 20% CD-PEG-DOX8 micelles preferentially accumulated in the mitochondria. Pharmacokinetic study showed area under the plasma concentration-time curve (AUC0-t) and Cmax for 20% CD-PEG-DOX8 micelles and DOX solution were 1336.58 ± 179.43 mg/L·h, 96.35 ± 3.32 mg/L and 1.40 ± 0.19 mg/L·h, 1.15 ± 0.25 mg/L, respectively. Biodistribution study showed the DOX concentration of 20% CD-PEG-DOX8 micelles treated group at 48 h was 2.37-fold higher than that of MeO-PEG-DOX8 micelles treated group at 48 h and was 24 fold-higher than that of DOX solution treated group at 24 h. CD-PEG-DOX8 micelles (20%) were well tolerated with reduced cardiotoxicity, as evaluated in the body weight change and HE staining studies, while they induced most significant antitumor activity with longest media survival time in an orthotopic mouse model of U87-luci glioblastoma model as displayed in the bioluminescence imaging and survival curve studies. Our findings consequently indicated that 20% CD-PEG-DOX8 micelles are promising drug delivery system for glioma chemotherapy. |
| Databáze: | OpenAIRE |
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