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Curr Drug Deliv. 2019;16(8):698-711. doi: 10.2174/1567201816666190828153017.

Crossing the Blood-Brain Barrier: A Review on Drug Delivery Strategies for Treatment of the Central Nervous System Diseases.

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Medical Genetics Unit, Department of Biomedical Science, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor, Malaysia.
Genetics & Regenerative Medicine Research Centre, Faculty of Medicine and Health Sciences, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor, Malaysia.
Department of Pharmaceutical Technology, Faculty of Pharmacy, International Islamic University Malaysia (IIUM), Kuantan, Malaysia.
IKOP Sdn. Bhd., Pilot Plant Pharmaceutical Manufacturing, Faculty of Pharmacy, IIUM, Kuantan, Malaysia.
International Institute of Halal Research & Training (INHART), IIUM, Kuala Lumpur, Malaysia.
UPM-MAKNA Cancer Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia, Serdang, Selangor, Malaysia.
Centre for Drug Research, Universiti Sains Malaysia, Gelugor, Penang, Malaysia.


Many drugs have been designed to treat diseases of the central nervous system (CNS), especially neurodegenerative diseases. However, the presence of tight junctions at the blood-brain barrier has often compromised the efficiency of drug delivery to target sites in the brain. The principles of drug delivery systems across the blood-brain barrier are dependent on substrate-specific (i.e. protein transport and transcytosis) and non-specific (i.e. transcellular and paracellular) transport pathways, which are crucial factors in attempts to design efficient drug delivery strategies. This review describes how the blood-brain barrier presents the main challenge in delivering drugs to treat brain diseases and discusses the advantages and disadvantages of ongoing neurotherapeutic delivery strategies in overcoming this limitation. In addition, we discuss the application of colloidal carrier systems, particularly nanoparticles, as potential tools for therapy for the CNS diseases.


Blood-brain barrier; central nervous system; colloidal carrier system; drug delivery system; nanoparticles; neurodegenerative diseases.

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