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Polymeric nanocarriers for nose-to-brain drug delivery in neurodegenerative diseases and neurodevelopmental disorders

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Acta Pharmaceutica Sinica B 2023年第5期13卷 1866-1886页

作者： Rania Awad Avi Avital Alejandro Sosnik Laboratory of Pharmaceutical Nanomaterials Science Department of Materials Science and EngineeringTechnion-Israel Institute of TechnologyHaifa 3200003Israel Behavioral Neurobiology Laboratory Department of Occupational TherapyFaculty of Social Welfare and Health SciencesUniversity of HaifaHaifa 3498838Israel

Neurodegenerative diseases are progressive conditions that affect the neurons of the central nervous system(CNS)and result in their damage and death.Neurodevelopmental disorders include intellectual disability,autism spectrum disorder,and attention-deficit/hyperactivity disorder and stem from the disruption of essential neurodevelopmental processes.The treatment of neurodegenerative and neurodevelopmental conditions,together affecting~120 million people worldwide,is challenged by the blood—brain barrier(BBB)and the blood—cerebrospinal fluid barrier that prevent the crossing of drugs from the systemic circulation into the CNS.The nose-to-brain pathway that bypasses the BBB and increases the brain bioavailability of intranasally administered drugs is promising to improve the treatment of CNS conditions.This pathway is more efficient for nanoparticles than for solutions,hence,the research on intranasal nano-drug delivery systems has grown exponentially over the last decade.Polymeric nanoparticles have become key players in the field owing to the high design and synthetic flexibility.This review describes the challenges faced for the treatment of neurodegenerative and neurodevelopmental conditions,the molecular and cellular features of the nasal mucosa and the contribution of intranasal nano-drug delivery to overcome them.Then,a comprehensive overview of polymeric nanocarriers investigated to increase drug bioavailability in the brain is introduced.

关键词： Neurodegenerative diseases Neurodevelopmental disorders Central nervous system Blood—brain barrier Nano-drug delivery systems Nose-to-brain pathway Intranasal administration Polymeric nanoparticles Polymeric micelles Dendrimers

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