Nanoodor Particles Deliver Drugs to Central Nervous System via Olfactory Pathway

Abstract Central nervous system (CNS) disorders confront significant challenges in drug delivery due to the blood–brain barrier (BBB). Inspired by the rapid and precise binding of odor molecules to olfactory receptors (ORs), this research uses thiolated HPMA to construct odor nanoparticles (nanoodor...

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Main Authors: Wei Zhang, Xingwang Ji, Qianyanqiu Zhao, Jinyao Qi, Wen Guo, Gaoshuo Zhang, Yujing Guan, Shenglong Li, Yuling Mao
Format: Article
Language:English
Published: Wiley 2025-04-01
Series:Advanced Science
Subjects:
Online Access:https://doi.org/10.1002/advs.202408908
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author Wei Zhang
Xingwang Ji
Qianyanqiu Zhao
Jinyao Qi
Wen Guo
Gaoshuo Zhang
Yujing Guan
Shenglong Li
Yuling Mao
author_facet Wei Zhang
Xingwang Ji
Qianyanqiu Zhao
Jinyao Qi
Wen Guo
Gaoshuo Zhang
Yujing Guan
Shenglong Li
Yuling Mao
author_sort Wei Zhang
collection DOAJ
description Abstract Central nervous system (CNS) disorders confront significant challenges in drug delivery due to the blood–brain barrier (BBB). Inspired by the rapid and precise binding of odor molecules to olfactory receptors (ORs), this research uses thiolated HPMA to construct odor nanoparticles (nanoodors) capable of delivering drugs to the CNS via the olfacto–cerebral pathway to overcome the delivery obstruction. The nanoodor core is used to encapsulate agomelatine (AGO), a CNS‐targeting antidepressant, and the encapsulation efficiency exceeded 80%. A series of thiol‐presenting nanoscale structures with different surface densities of thiol groups are constructed, and the effectiveness positively correlated with the density of thiol groups on their surface. Notably, the nanoodors enable precise brain‐targeted delivery, outperforming commercially available oral formulations in terms of drug accumulation in the brain and antidepressant effects. The study of the nanoodor transport and action mechanisms revealed that after binding to ORs, the nanoodors are rapidly delivered to the brain via the olfactory pathway. Nanoodors, the first design to deliver CNS drugs via the olfactory pathway by mimicking natural smells for the treatment of CNS disorders, are expected to achieve clinical transformation, benefiting human health.
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issn 2198-3844
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spelling doaj-art-85cd98149ab0418fa67b9b732e18eab72025-08-20T02:26:45ZengWileyAdvanced Science2198-38442025-04-011215n/an/a10.1002/advs.202408908Nanoodor Particles Deliver Drugs to Central Nervous System via Olfactory PathwayWei Zhang0Xingwang Ji1Qianyanqiu Zhao2Jinyao Qi3Wen Guo4Gaoshuo Zhang5Yujing Guan6Shenglong Li7Yuling Mao8Department of Pharmaceutics School of Pharmacy Shenyang Pharmaceutical University 103 Wenhua Road Shenyang Liaoning 110016 P. R. ChinaDepartment of Pharmaceutics School of Pharmacy Shenyang Pharmaceutical University 103 Wenhua Road Shenyang Liaoning 110016 P. R. ChinaDepartment of Pharmaceutics School of Pharmacy Shenyang Pharmaceutical University 103 Wenhua Road Shenyang Liaoning 110016 P. R. ChinaDepartment of Pharmaceutics School of Pharmacy Shenyang Pharmaceutical University 103 Wenhua Road Shenyang Liaoning 110016 P. R. ChinaDepartment of Pharmaceutics School of Pharmacy Shenyang Pharmaceutical University 103 Wenhua Road Shenyang Liaoning 110016 P. R. ChinaDepartment of Pharmaceutics School of Pharmacy Shenyang Pharmaceutical University 103 Wenhua Road Shenyang Liaoning 110016 P. R. ChinaInstitute of Cancer Medicine Faculty of Medicine Dalian University of Technology No.2 Linggong Road, Ganjingzi District Dalian Liaoning 116024 ChinaSecond Ward of Bone and Soft Tissue Tumor Surgery Cancer Hospital of Dalian University of Technology Cancer Hospital of China Medical University Liaoning Cancer Hospital & Institute Shenyang Liaoning 110042 ChinaDepartment of Pharmaceutics School of Pharmacy Shenyang Pharmaceutical University 103 Wenhua Road Shenyang Liaoning 110016 P. R. ChinaAbstract Central nervous system (CNS) disorders confront significant challenges in drug delivery due to the blood–brain barrier (BBB). Inspired by the rapid and precise binding of odor molecules to olfactory receptors (ORs), this research uses thiolated HPMA to construct odor nanoparticles (nanoodors) capable of delivering drugs to the CNS via the olfacto–cerebral pathway to overcome the delivery obstruction. The nanoodor core is used to encapsulate agomelatine (AGO), a CNS‐targeting antidepressant, and the encapsulation efficiency exceeded 80%. A series of thiol‐presenting nanoscale structures with different surface densities of thiol groups are constructed, and the effectiveness positively correlated with the density of thiol groups on their surface. Notably, the nanoodors enable precise brain‐targeted delivery, outperforming commercially available oral formulations in terms of drug accumulation in the brain and antidepressant effects. The study of the nanoodor transport and action mechanisms revealed that after binding to ORs, the nanoodors are rapidly delivered to the brain via the olfactory pathway. Nanoodors, the first design to deliver CNS drugs via the olfactory pathway by mimicking natural smells for the treatment of CNS disorders, are expected to achieve clinical transformation, benefiting human health.https://doi.org/10.1002/advs.202408908AgomelatineBrain targetingCentral nervous system disordersNanoodor particlesOlfactory pathway
spellingShingle Wei Zhang
Xingwang Ji
Qianyanqiu Zhao
Jinyao Qi
Wen Guo
Gaoshuo Zhang
Yujing Guan
Shenglong Li
Yuling Mao
Nanoodor Particles Deliver Drugs to Central Nervous System via Olfactory Pathway
Advanced Science
Agomelatine
Brain targeting
Central nervous system disorders
Nanoodor particles
Olfactory pathway
title Nanoodor Particles Deliver Drugs to Central Nervous System via Olfactory Pathway
title_full Nanoodor Particles Deliver Drugs to Central Nervous System via Olfactory Pathway
title_fullStr Nanoodor Particles Deliver Drugs to Central Nervous System via Olfactory Pathway
title_full_unstemmed Nanoodor Particles Deliver Drugs to Central Nervous System via Olfactory Pathway
title_short Nanoodor Particles Deliver Drugs to Central Nervous System via Olfactory Pathway
title_sort nanoodor particles deliver drugs to central nervous system via olfactory pathway
topic Agomelatine
Brain targeting
Central nervous system disorders
Nanoodor particles
Olfactory pathway
url https://doi.org/10.1002/advs.202408908
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