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

Mithramycin encapsulated in polymeric micelles by microfluidic technology as novel therapeutic protocol for beta-thalassemia
Mithramycin encapsulated in polymeric micelles by microfluidic technology as novel therapeutic protocol for beta-thalassemia
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 ?-globin messenger ribonucleic acid production and to increase fetal hemoglobin (HbF) accumulation, the percentage of HbF-containing cells, and their HbF content without stimulating ?-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.

1176-9114
307-324
Capretto, Lorenzo
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Mazzitelli, Stefania
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Brognara, Eleonora
8e06fa7c-60ff-472e-ae2e-e692ec0b441b
Lampronti, Ilaria
74550c2b-2219-4849-a8e5-1d8a0d8c15c6
Carugo, Dario
0a4be6cd-e309-4ed8-a620-20256ce01179
Hill, Martyn
0cda65c8-a70f-476f-b126-d2c4460a253e
Zhang, Xunli
d7cf1181-3276-4da1-9150-e212b333abb1
Gambari, Roberto
b8e3f7f3-1a34-4193-b78b-3f5beb9a4650
Nastruzzi, Claudio
fa760f44-1546-4aa2-838d-242a908ea463
Capretto, Lorenzo
0f3586b5-1560-49c1-a76b-59e74ea600ef
Mazzitelli, Stefania
d9923ab4-b354-4b9e-87d1-f67d86e1a8dc
Brognara, Eleonora
8e06fa7c-60ff-472e-ae2e-e692ec0b441b
Lampronti, Ilaria
74550c2b-2219-4849-a8e5-1d8a0d8c15c6
Carugo, Dario
0a4be6cd-e309-4ed8-a620-20256ce01179
Hill, Martyn
0cda65c8-a70f-476f-b126-d2c4460a253e
Zhang, Xunli
d7cf1181-3276-4da1-9150-e212b333abb1
Gambari, Roberto
b8e3f7f3-1a34-4193-b78b-3f5beb9a4650
Nastruzzi, Claudio
fa760f44-1546-4aa2-838d-242a908ea463

Capretto, Lorenzo, Mazzitelli, Stefania, Brognara, Eleonora, Lampronti, Ilaria, Carugo, Dario, Hill, Martyn, Zhang, Xunli, Gambari, Roberto and Nastruzzi, Claudio (2012) Mithramycin encapsulated in polymeric micelles by microfluidic technology as novel therapeutic protocol for beta-thalassemia. International Journal of Nanomedicine, 7, 307-324. (doi:10.2147/IJN.S25657).

Record type: Article

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 ?-globin messenger ribonucleic acid production and to increase fetal hemoglobin (HbF) accumulation, the percentage of HbF-containing cells, and their HbF content without stimulating ?-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.

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IJN-25657-mithramycin-encapsulated-in-polymeric-micelles-by-microfluid_011712_11843.pdf - Version of Record
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Published date: January 2012
Organisations: Engineering Science Unit

Identifiers

Local EPrints ID: 208455
URI: https://eprints.soton.ac.uk/id/eprint/208455
ISSN: 1176-9114
PURE UUID: d852d7e7-6a81-4104-893b-4a461e0cc8ad
ORCID for Martyn Hill: ORCID iD orcid.org/0000-0001-6448-9448

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Date deposited: 19 Jan 2012 15:05
Last modified: 06 Jun 2018 13:12

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