Enriched chitosan nanoparticles loaded with siRNA are effective in lowering Huntington's disease gene expression following intranasal administration

Publication date: Available online 27 October 2019Source: Nanomedicine: Nanotechnology, Biology and MedicineAuthor(s): Vasyl Sava, Oksana Fihurka, Anastasia Khvorova, Juan Sanchez-RamosAbstractTherapies to lower gene expression in brain disease currently require chronic administration into the cerebrospinal fluid (CSF) by intrathecal infusions or direct intracerebral injections. Though well-tolerated in the short-term, this approach is not tenable for a life-time of administration. Nose-to-brain delivery of enriched chitosan-based nanoparticles loaded with anti-HTT siRNA was studied in a transgenic YAC128 mouse model of Huntington's Disease (HD). A series of chitosan-based nanoparticle (NP) formulations encapsulating anti-HTT small interfering RNA (siRNA) were designed to protect the payload from degradation “en route” to the target. Factors to improve production of effective nanocarriers of anti-HTT siRNA were identified and tested in a YAC128 mouse model of Huntington's disease. Four formulations of nanocarriers were identified to be effective in lowering HTT mRNA expression by at least 50%. Intranasal administration of nanoparticles carrying siRNA is a promising therapeutic alternative for safe and effective lowering of mutant HTT expression.Graphical AbstractA)Nanoparticles (NP) were synthesized by polyelectrolyte complexation of chitosan (CS) with anti-HTT siRNA and matrices were cross-linked with Mangafodipir. Flow chart of NP fabrication. P = provisional ...
Source: Nanomedicine: Nanotechnology, Biology and Medicine - Category: Nanotechnology Source Type: research