RT Journal Article T1 Evaluation of poly(N-ethyl pyrrolidine methacrylamide) (EPA) and derivatives as polymeric vehicles for miRNA delivery to neural cells A1 Soto, Altea A1 Nieto Díaz, Manuel A1 Martínez Campos, Enrique A1 Noalles Dols, Ana A1 Barreda Manso, María Asunción A1 Reviriego, Felipe A1 Reinecke, Helmut A1 Reigada, David A1 Muñoz Galdeano, Teresa A1 Novillo, Irene A1 Gallardo, Alberto A1 Rodríguez Hernández, Juan A1 Eritja, Ramón A1 Aviñó, Anna A1 Elvira, Carlos A1 Maza, Rodrigo M. AB MicroRNAs (miRNAs) are endogenous, short RNA oligonucleotides that regulate the expression of hundreds of proteins to control cells’ function in physiological and pathological conditions. miRNA therapeutics are highly specific, reducing the toxicity associated with off-target effects, and require low doses to achieve therapeutic effects. Despite their potential, applying miRNA-based therapies is limited by difficulties in delivery due to their poor stability, fast clearance, poor efficiency, and off-target effects. To overcome these challenges, polymeric vehicles have attracted a lot of attention due to their ease of production with low costs, large payload, safety profiles, and minimal induction of the immune response. Poly(N-ethyl pyrrolidine methacrylamide) (EPA) copolymers have shown optimal DNA transfection efficiencies in fibroblasts. The present study aims to evaluate the potential of EPA polymers as miRNA carriers for neural cell lines and primary neuron cultures when they are copolymerized with different compounds. To achieve this aim, we synthesized and characterized different copolymers and evaluated their miRNA condensation ability, size, charge, cytotoxicity, cell binding and internalization ability, and endosomal escape capacity. Finally, we evaluated their miRNA transfection capability and efficacy in Neuro-2a cells and rat primary hippocampal neurons. The results indicate that EPA and its copolymers, incorporating β-cyclodextrins with or without polyethylene glycol acrylate derivatives, can be promising vehicles for miRNA administration to neural cells when all experiments on Neuro-2a cells and primary hippocampal neurons are considered together. PB MDPI SN 1999-4923 YR 2023 FD 2023-05-10 LK https://hdl.handle.net/20.500.14352/115306 UL https://hdl.handle.net/20.500.14352/115306 LA eng NO Soto, A.; Nieto-Díaz, M.; Martínez-Campos, E.; Noalles-Dols, A.; Barreda-Manso, M.A.; Reviriego, F.; Reinecke, H.; Reigada, D.; Muñoz-Galdeano, T.; Novillo, I.; et al. Evaluation of Poly(N-Ethyl Pyrrolidine Methacrylamide) (EPA) and Derivatives as Polymeric Vehicles for miRNA Delivery to Neural Cells. Pharmaceutics 2023, 15, 1451. https://doi.org/10.3390/pharmaceutics15051451 NO 2023 Descuento MDPI NO Comunidad de Castilla-La Mancha NO European Commission NO Ministerio de Ciencia, Innovación y Universidades (España) DS Docta Complutense RD 12 abr 2025