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2 results on '"human erythroid precursor cells"'

1. Mithramycin encapsulated in polymeric micelles by microfluidic technology as novel therapeutic protocol for beta-thalassemia.

Author

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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2. Mithramycin encapsulated in polymeric micelles by microfluidic technology as novel therapeutic protocol for beta-thalassemia

Author

Dario Carugo, Lorenzo Capretto, Stefania Mazzitelli, Roberto Gambari, Eleonora Brognara, Martyn Hill, Claudio Nastruzzi, Ilaria Lampronti, and Xunli Zhang

Subjects
Drug, Medicine (General), Erythrocytes, Polymers, Chemistry, Pharmaceutical, media_common.quotation_subject, Cellular differentiation, Microfluidics, Biophysics, Pharmaceutical Science, Bioengineering, Biology, Micelle, Biomaterials, R5-920, human erythroid precursor cells, International Journal of Nanomedicine, Lab-On-A-Chip Devices, hemic and lymphatic diseases, Drug Discovery, Fetal hemoglobin, medicine, Humans, Cells, Cultured, Micelles, Erythroid Precursor Cells, Original Research, media_common, erythroid differentiation, Analysis of Variance, Plicamycin, lab-on-a-chip, beta-Thalassemia, fungi, Organic Chemistry, Reproducibility of Results, Cell Differentiation, General Medicine, Poloxamer, Molecular biology, design of experiments, K562 Cells, K562 cells, medicine.drug
Abstract

Lorenzo Capretto1, Stefania Mazzitelli2, Eleonora Brognara2, Ilaria Lampronti2, Dario Carugo1, Martyn Hill1, Xunli Zhang1, Roberto Gambari2, Claudio Nastruzzi31Engineering Sciences, University of Southampton, Southampton, UK; 2Department of Biochemistry and Molecular Biology, 3Department of Pharmaceutical Sciences, University of Ferrara, Ferrara, ItalyAbstract: 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 ß-thalassemia. These results represent an important first step toward a potential clinical application, since an increase in HbF could alleviate the symptoms underlying ß-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 ß-thalassemia.Keywords: microfluidics, lab-on-a-chip, design of experiments, erythroid differentiation, human erythroid precursor cells

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