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Microspheres containing insulin-like growth factor I for treatment of chronic neurodegeneration

AutorCarrascosa, Carlos; Torres Alemán, Ignacio ; López-López, C.; Carro, E.; Espejo, L.; Torrado, Susana; Torrado, Juan J.
Palabras claveMicrosphere PLGA IGF-I Pharmacokinetic Neurodegeneration
Fecha de publicación2004
EditorPergamon Press
CitaciónBiomaterials 25: 707- 714 (2004)
ResumenThe therapeutic potential of peptide growth factors as insulin-like growth factor I (IGF-I) is currently under intense scrutiny in a wide variety of diseases, including neurodegenerative illnesses. A new poly(lactic-co-glycolide) -based microsphere IGF-I controlled release formulation for subcutaneous (SC) delivery has been developed by a triple emulsion method. The resulting microspheres displayed a mean diameter of 1.5μm, with an encapsulation efficiency of 74.3%. The protein retained integrity after the microencapsulation process as evaluated by circular dichroism and SDS-PAGE. The administration of IGF-I in microspheres caused at least a 30-fold increase in IGF-I mean residence time in rats and mice when compared with the conventional SC solution. Therefore, dosing can be changed from the conventional twice a day to once every 2 weeks. Therapeutic efficacy of this new formulation has been studied in mutant mice with inherited Purkinje cell degeneration (PCD). These mice show a chronic limb discoordination that is resolved after continuous systemic delivery of IGF-I. Normal motor coordination was maintained as long as IGF-I microsphere therapy is continued. Moreover, severely affected PCD mice, with marked ataxia, muscle wasting and shortened life-span showed a significant improvement after continuous IGF-I microsphere therapy as determined by enhanced motor coordination, marked weight gain and extended survival. This new formulation can be considered of great therapeutic promise for some chronic brain diseases. © 2003 Elsevier Ltd. All rights reserved.
Identificadoresdoi: 10.1016/S0142-9612(03)00562-3
issn: 0142-9612
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