Hernan Cortes, Sergio Alcala-Alcala, Arturo Avalos-Fuentes, Nestor Mendoza-Munoz, David Quintanar-Guerrero, Gerardo Leyva-Gomez* and Benjamin Floran* Pages 1866 - 1879 ( 14 )
Background: The lack of an outright treatment for Parkinson’s disease (PD) is a pivotal concern in medicine and has driven the search for novel alternatives for treating the disease. Among the proposed approaches, small interfering RNA (siRNA)-based therapy is attracting significant attention as a potential method for the treatment of PD; however, siRNAs delivery possesses potential drawbacks, such as reduced stability in blood circulation and low capacity for reaching the target site.
Objective: This review aims to explore siRNA-based approaches to PD and the latest advances for designing nanoparticles that effectively target siRNAs to the action site and that protect these against degradation in blood circulation.
Results: siRNA-based approaches provide an interesting option for designing new strategies for treating PD through the silencing of genes, whose abnormal expressions contribute to the pathophysiology of the disease; however, siRNA delivery to the brain is a key issue that remains unsolved to date. Current research efforts are focused on designing vectors that effectively transport and protect siRNAs. In this regard, nanoparticles are being developed as carriers for siRNAs with controlled delivery efficiency and low toxicity profiles, and these represent an alternative to common vectors.
Conclusion: Identification of putative gene targets for siRNA therapy of PD has set the pace for researching non-viral vectors; however, the technological aspects for tackling the challenge that siRNAs targeting to the brain represents are essentials. In this respect, the formulation of siRNAs in nanoparticles would avoid harmful side effects, such as immunogenic and oncogenic drawbacks.
Parkinson's disease treatment, siRNA therapy, nanoparticle-based delivery of siRNA, siRNA drug targeting, blood-brain barrier, nanotechnology.
Laboratory of Genomic Medicine, Department of Genetics, Instituto Nacional de Rehabilitacion Luis Guillermo Ibarra Ibarra, Mexico City, Laboratorio de Tecnología Farmaceutica, Facultad de Farmacia, Universidad Autonoma del Estado de Morelos, Cuernavaca, Morelos, Department of Physiology, Biophysics & Neuroscience, Centro de Investigacion y de Estudios Avanzados del Instituto Politecnico Nacional (CINVESTAV-IPN), Mexico City, Laboratorio de Farmacia, Facultad de Ciencias Quimicas, Universidad de Colima, Carr. Colima-Coquimatlan km 9, Coquimatlan, Colima, Facultad de Estudios Superiores Cuautitlan, Universidad Nacional Autonoma de Mexico (UNAM), Laboratorio de Posgrado en Tecnologia Farmaceutica, Av. 1o de mayo s/n, Cuautitlan Izcalli, Edo de Mexico, Laboratory of Connective Tissue, Centro Nacional de Investigacion y Atencion de Quemados, Instituto Nacional de Rehabilitacion Luis Guillermo Ibarra Ibarra, Codigo Postal 14389, CDMX, Department of Physiology, Biophysics & Neuroscience, Centro de Investigacion y de Estudios Avanzados del Instituto Politecnico Nacional, Apartado Postal 14-740, 07000 CDMX