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.

Microfluidic-Assisted Preparation of Targeted pH-Responsive Polymeric Micelles Improves Gemcitabine Effectiveness in PDAC: In Vitro Insights

“…In addition, to improve specific targeting to the PDAC, the surface of such micelles was properly functionalized with a selective ligand for uPAR receptor, which is highly expressed in PDAC cells [ 12 , 13 ], such as the peptide AE105 [ 5 ]. The microfluidic technique has already been successfully employed to control the size, shape, and polydispersity of polymeric micelles [ 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 ]; however, to the best of our knowledge, there have been few reports on microfluidics-based pH-responsive polymeric micellar delivery systems [ 37 , 38 , 39 ] and no one has applied these to PDAC cancer research. In particular, Feng et al [ 37 ] obtained the pH-responsive micelles by mixing two different block copolymers (the PLGA and the poly(ethylene glycol)-poly(2-(diisopropylamino)ethyl methacrylate(PEG-b-PDPA)); additionally, Albuquerque et al [ 38 ], using the poly([N-(2-hydroxypropyl)]methacrylamide)-bpoly [2-(diisopropylamino)ethyl methacrylate] (PHPMAm-b-PDPAn), blocked copolymers, thus obtaining quasi-monodisperse assemblies, characterized by more consistent biodistribution and cellular uptake.…”