title: Mithramycin encapsulated in polymeric micelles by microfluidic technology as novel therapeutic protocol for beta-thalassemia.
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.
authors.affiliation: Engineering Sciences, University of Southampton, Southampton, UK.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Capretto
authors.forename: Stefania
authors.initials: S
authors.lastname: Mazzitelli
authors.forename: Eleonora
authors.initials: E
authors.lastname: Brognara
authors.forename: Ilaria
authors.initials: I
authors.lastname: Lampronti
authors.forename: Dario
authors.initials: D
authors.lastname: Carugo
authors.forename: Martyn
authors.initials: M
authors.lastname: Hill
authors.forename: Xunli
authors.initials: X
authors.lastname: Zhang
authors.forename: Roberto
authors.initials: R
authors.lastname: Gambari
authors.forename: Claudio
authors.initials: C
authors.lastname: Nastruzzi
mesh_terms: D000704:Analysis of Variance; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D004912:Erythrocytes / Q000187:drug effects / Q000473:pathology; D015672:Erythroid Precursor Cells; D006801:Humans; D020014:K562 Cells / Q000187:drug effects; D056656:Lab-On-A-Chip Devices; D008823:Micelles; D044085:Microfluidics; D008926:Plicamycin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry; D011108:Polymers; D015203:Reproducibility of Results; D017086:beta-Thalassemia / Q000188:drug therapy*
chemical_list: D008823:Micelles; D011108:Polymers; C066851:mithramycin A; D008926:Plicamycin