1. Mithramycin encapsulated in polymeric micelles by microfluidic technology as novel therapeutic protocol for beta-thalassemia.
- Author
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Capretto L, Mazzitelli S, Brognara E, Lampronti I, Carugo D, Hill M, Zhang X, Gambari R, and Nastruzzi C
- Subjects
- Analysis of Variance, Cell Differentiation drug effects, Cells, Cultured, Erythrocytes drug effects, Erythrocytes pathology, Erythroid Precursor Cells, Humans, K562 Cells drug effects, Lab-On-A-Chip Devices, Plicamycin administration & dosage, Plicamycin chemistry, Reproducibility of Results, Chemistry, Pharmaceutical methods, Micelles, Microfluidics, Plicamycin analogs & derivatives, Polymers, beta-Thalassemia drug therapy
- Abstract
This report shows that the DNA-binding drug, mithramycin, can be efficiently encapsulated in polymeric micelles (PM-MTH), based on Pluronic(®) block copolymers, by a new microfluidic approach. The effect of different production parameters has been investigated for their effect on PM-MTH characteristics. The compared analysis of PM-MTH produced by microfluidic and conventional bulk mixing procedures revealed that microfluidics provides a useful platform for the production of PM-MTH with improved controllability, reproducibility, smaller size, and polydispersity. Finally, an investigation of the effects of PM-MTH, produced by microfluidic and conventional bulk mixing procedures, on the erythroid differentiation of both human erythroleukemia and human erythroid precursor cells is reported. It is demonstrated that PM-MTH exhibited a slightly lower toxicity and more pronounced differentiative activity when compared to the free drug. In addition, PM-MTH were able to upregulate preferentially γ-globin messenger ribonucleic acid production and to increase fetal hemoglobin (HbF) accumulation, the percentage of HbF-containing cells, and their HbF content without stimulating α-globin gene expression, which is responsible for the clinical symptoms of β-thalassemia. These results represent an important first step toward a potential clinical application, since an increase in HbF could alleviate the symptoms underlying β-thalassemia and sickle cell anemia. In conclusion, this report suggests that PM-MTH produced by microfluidic approach warrants further evaluation as a potential therapeutic protocol for β-thalassemia.
- Published
- 2012
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