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Critical Reviews™ in Therapeutic Drug Carrier Systems
IF: 2.414 5-Year IF: 3.324 SJR: 0.573 SNIP: 0.551 CiteScore™: 2.43

ISSN Print: 0743-4863
ISSN Online: 2162-660X

Critical Reviews™ in Therapeutic Drug Carrier Systems

DOI: 10.1615/CritRevTherDrugCarrierSyst.2018024697
pages 433-467

Updated Progress of Nanocarrier-Based Intranasal Drug Delivery Systems for Treatment of Brain Diseases

Ying Fan
Chongqing Key Laboratory of Natural Product Synthesis and Drug Research, School of Pharmaceutical Sciences, Chongqing University, Chongqing 401331, P.R. China
Min Chen
Chongqing Key Laboratory of Natural Product Synthesis and Drug Research, School of Pharmaceutical Sciences, Chongqing University, Chongqing 401331, P.R. China
Jinqiang Zhang
Chongqing Key Laboratory of Natural Product Synthesis and Drug Research, School of Pharmaceutical Sciences, Chongqing University, Chongqing 401331, P.R. China
Philippe Maincent
Universite de Lorraine, CITHEFOR EA 3452, Faculte de Pharmacie, BP 80403, F-54001 Nancy Cedex, France
Xuefeng Xia
Chongqing Key Laboratory of Natural Product Synthesis and Drug Research, School of Pharmaceutical Sciences, Chongqing University, Chongqing 401331, P.R. China
Wen Wu
Chongqing Key Laboratory of Natural Product Synthesis and Drug Research, School of Pharmaceutical Sciences, Chongqing University, Chongqing 401331, P.R. China

ABSTRACT

Intranasal drug delivery is emerging as a reliable and promising pathway to deliver a wide range of therapeutic agents including small and large molecules, peptides and proteins, genes to the central nervous system for the treatment of brain diseases such as Alzheimer's disease, Parkinson’s disease, depression, migraine, schizophrenia, and glioma. This presents noninvasive entry into the brain via direct nose-to-brain and/or indirect nose-to-blood-to-brain routes. Several nanocarrier-based strategies have been developed to transport therapeutic agents to the brain including nanoparticles, liposomes, and exosomes following intranasal delivery. However, the multiple barriers in nose-to-brain route — including rapid mucociliary clearance in the nasal cavity, enzyme degradation, and the blood–brain barrier (BBB) — pose serious challenges to brain-targeted drug delivery. Hence, very limited translation from the laboratory to the clinic has been achieved. The present review highlights the surface modification of nanocarriers with different strategies devoted to facilitate nose-to-brain delivery: prolonging retention time in the nasal cavity, improving penetration ability, and promoting brain targeting with ligands. Additionally, in vitro blood–brain barrier models, influencing an efficient study on intranasal delivery of therapeutics into the brain through indirect nose-to-blood-to-brain pathway, is discussed.