Nanocarriers loaded with siRNA can be administered intranasally to provide a noninvasive, safe alternative to direct intracerebral or intrathecal infusions to reach the brain or the cerebrospinal fluid (CSF). Dual-function nanocarriers can also be designed to deliver several payloads that address different components of the pathological process.
Our inventors developed a novel multifunctional hybrid nanocarrier capable of carrying dual payloads for delivery and treatment of neurological diseases. Hybrid nanoparticles are composed of a chitosan (CS)–siRNA core matrix and laminated with a lipid shell containing cannabidiol (CBD). The nanocarriers maintain a small particle size (range: 150–210 nm) and ensures efficient encapsulation of payload, while minimizing potential cell cytotoxicity. Through non-invasive nose-to-brain delivery, the nanocarriers effectively navigate the blood-brain barrier, facilitating precise targeting.
This nanocarrier system was developed for treating the mutated gene in Huntington's disease (HD), HTT, but it is applicable to other neurological indications. Preclinical research showed that the nanocarrier, which was composed of a CS core loaded with novel anti-HTT siRNA and a lipid shell containing CBD, effectively lowered HTT expression and decreased levels of the inflammatory cytokine IL-6 in mesenchymal stem cell cultures obtained from a YAC128 transgenic mouse modeling Huntington’s disease. This technology holds potential for enhancing medical treatments for various neurological disorders and offers new prospects for targeted gene therapy, driving advancements in neuroscience.
Top: Hybrid Nanoparticle Design
Bottom: In vitro gene silencing efficacy of anti-HTT siRNAs packaged into chitosan lactate-based nanoparticles and hybrid nanoparticles. CSL: Chitosan lactate; HNP: Hybrid nanoparticle; NP: Nanoparticle.