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Development of surface modified biodegradable polymeric nanoparticles to deliver GSE24.2 peptide to cells: A promising approach for the treatment of defective telomerase disorders

AutorEgusquiaguirre, Susana P.; Manguan-García, Cristina ; Pintado-Berninches, Laura ; Perona Abellón, Rosario ; Igartua, Manuela
Fecha de publicación2015
CitaciónEuropean Journal of Pharmaceutics and Biopharmaceutics 91: 91-102 (2015)
ResumenThe aim of the present study was to develop a novel strategy to deliver intracellularly the peptide GSE24.2 for the treatment of Dyskeratosis congenita (DC) and other defective telomerase disorders. For this purpose, biodegradable polymeric nanoparticles using poly(lactic-co-glycolic acid) (PLGA NPs) or poly(lactic-co-glycolic acid)-poly ethylene glycol (PLGA-PEG NPs) attached to either polycations or cell-penetrating peptides (CPPs) were prepared in order to increase their cellular uptake. The particles exhibited an adequate size and zeta potential, with good peptide loading and a biphasic pattern obtained in the in vitro release assay, showing an initial burst release and a later sustained release. GSE24.2 structural integrity after encapsulation was assessed using SDS-PAGE, revealing an unaltered peptide after the NPs elaboration. According to the cytotoxicity results, cell viability was not affected by uncoated polymeric NPs, but the incorporation of surface modifiers slightly decreased the viability of cells. The intracellular uptake exhibited a remarkable improvement of the internalization, when the NPs were conjugated to the CPPs. Finally, the bioactivity, addressed by measuring DNA damage rescue and telomerase reactivation, showed that some formulations had the lowest cytotoxicity and highest biological activity. These results proved that GSE24.2-loaded NPs could be delivered to cells, and therefore, become an effective approach for the treatment of DC and other defective telomerase syndromes.
Descripciónet al.
Identificadoresdoi: 10.1016/j.ejpb.2015.01.028
issn: 0939-6411
e-issn: 1873-3441
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