Kinetics of HTT lowering in brain of YAC 128 mice following single and repetitive intranasal dosing of siRNA packaged in chitosan-based nanoparticles

Sava, Vasyl; Fihurka, Oksana; Khvorova, Anastasia; Sanchez‐Ramos, Juan

doi:10.1016/j.jddst.2021.102517

Cited by 7 publications

(10 citation statements)

References 19 publications

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“…Employing mathematical modeling, these nanoparticles helped establish dosing schedules that effectively lower therapeutic gene expression. This approach elucidated the kinetics and cumulative effects of multiple intranasal administrations, aiding in the prediction and optimization of dosing schedules for therapeutic gene suppression [ 127 ]. siRNA-loaded chitosan nanoparticles targeting galectin-1 for glioblastoma were designed to deliver siRNA targeting galectin-1 intranasally, achieving rapid delivery to the central nervous system and significant reduction in Gal-1 expression in tumor cells.…”

Section: Specific Treatment and Conditionsmentioning

confidence: 99%

“…Furthermore, disease-specific testing is vital for targeted therapeutic applications, such as in models of Alzheimer’s disease, asthma, schizophrenia, and other conditions. These tests help establish the efficacy of nanoparticles in treating specific diseases and understanding their interactions within disease-specific contexts [ 36 , 45 , 117 , 118 , 121 , 124 , 126 , 127 , 128 ].…”

Section: Testingmentioning

confidence: 99%

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Chitosan Nanoparticles for Intranasal Drug Delivery

Omidian,

Gill,

Dey Chowdhury

et al. 2024

Pharmaceutics

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This manuscript explores the use of nanostructured chitosan for intranasal drug delivery, targeting improved therapeutic outcomes in neurodegenerative diseases, psychiatric care, pain management, vaccination, and diabetes treatment. Chitosan nanoparticles are shown to enhance brain delivery, improve bioavailability, and minimize systemic side effects by facilitating drug transport across the blood–brain barrier. Despite substantial advancements in targeted delivery and vaccine efficacy, challenges remain in scalability, regulatory approval, and transitioning from preclinical studies to clinical applications. The future of chitosan-based nanomedicines hinges on advancing clinical trials, fostering interdisciplinary collaboration, and innovating in nanoparticle design to overcome these hurdles and realize their therapeutic potential.

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Section: Specific Treatment and Conditionsmentioning

confidence: 99%

Section: Testingmentioning

confidence: 99%

Chitosan Nanoparticles for Intranasal Drug Delivery

Omidian,

Gill,

Dey Chowdhury

et al. 2024

Pharmaceutics

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show abstract

“…One such modification is the conjugation of chitosan, a mucoadhesive agent which functions by electrostatically interacting with the negatively charged epithelial surfaces and thus enhancing the drug’s duration of stay in the nasal cavity ( Maher et al, 2023 ). A study exploring the intranasal administration of a chitosan-based nanoparticle containing HTT targeting siRNA demonstrated therapeutically significant lowering of HTT mRNA in the mouse brain ( Sava et al, 2021 ). Another method to increase drug residence time in the nasal cavity is through the use of biogels, which are liquids that transition to gels at body temperature ( Thakkar et al, 2021 ).…”

Section: Cns Administration Techniquesmentioning

confidence: 99%

Nucleic acid-based therapeutics for the treatment of central nervous system disorders

McCartan,

Khorkova,

Volmar

et al. 2023

Front. Genet.

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Nucleic acid-based therapeutics (NBTs) are an emerging class of drugs with potential for the treatment of a wide range of central nervous system conditions. To date, pertaining to CNS indications, there are two commercially available NBTs and a large number of ongoing clinical trials. However, these NBTs are applied directly to the brain due to very low blood brain barrier permeability. In this review, we outline recent advances in chemical modifications of NBTs and NBT delivery techniques intended to promote brain exposure, efficacy, and possible future systemic application.

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“…The kinetics of consequent lowering of target gene expression is important for determining dosing frequency and intervals that would be expected to achieve a therapeutic magnitude and duration of effect. Prior reports have described such kinetics, but none have examined an intranasal delivery route [27][28][29][30]. We sought to develop a mathematical model of the kinetics of our intranasally delivered nanocarrier and compare this to in vivo performance in a transgenic mouse model of HD (YAC 128 mice bearing human mHTT).…”

Section: Kinetic Control Of Repetitive Intranasal Dosingmentioning

confidence: 99%

Key Features in the Design and Function of Nanocarriers for Intranasal Administration of Gene Therapy in Huntington Disease

Fihurka,

Aradi,

Sava

et al. 2023

J Nanotechnol Nanomaterials

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A major obstacle to fulfilling the therapeutic promise of gene therapies for hereditary brain diseases, such as Huntington’ Disease (HD), is the requirement for viral vectors and/or an invasive delivery system (stereotaxic injection into brain or infusion into the intrathecal space). HD is an autosomal dominant neurodegenerative disease for which several clinical trials have demonstrated gene-lowering effects following intrathecal administration. These technical limitations have given impetus to the development of alternative non-invasive delivery systems for gene therapy of brain diseases. The overall objective of this review is to discuss the key features in the design of nanocarriers for intranasal administration of gene-therapy for HD, focusing primarily on our series of published work on the use of nanocarriers for gene therapy. Design and development of nanocarriers packaged with gene-lowering agents represents a significant advance towards non-invasive nose-to-brain delivery of gene therapy for HD and other hereditary brain disorders.

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Kinetics of HTT lowering in brain of YAC 128 mice following single and repetitive intranasal dosing of siRNA packaged in chitosan-based nanoparticles

Cited by 7 publications

References 19 publications

Chitosan Nanoparticles for Intranasal Drug Delivery

Chitosan Nanoparticles for Intranasal Drug Delivery

Nucleic acid-based therapeutics for the treatment of central nervous system disorders

Key Features in the Design and Function of Nanocarriers for Intranasal Administration of Gene Therapy in Huntington Disease

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