Current Drug Therapy Send Orders for Reprints to reprints@benthamscience.ae 4 Current Drug Therapy, 2018, 13, 4-24 REVIEW ARTICLE Advances in Drug Delivery from Nose to Brain: An Overview Rajashree S. Hirlekar * and Alfiha M. Momin Department of Pharmaceutics, Vivekanand Education Society’s College of Pharmacy, Hashu Advani, Memorial Complex, Behind Collector Colony, Chembur (E) Mumbai-400074, Maharashtra, India Abstract: Brain targeting has always been challenging due to the presence of various physiological barriers resulting in low bioavailability via the oral and parenteral route. Altering the integrity of these barriers so as to permit the drugs to enter into the brain could severely damage the Central Nervous System by also allowing the entrance of toxic substances, bacteria and viruses into the brain. This problem can be tackled by delivering drugs via the intranasal route which bypasses the blood brain barrier and reaches different parts of the brain primarily via the olfactory and trigeminal neural pathways. This route offers several advantages over the oral and parenteral route and has shown potential for targeting drugs to the brain for treating various central nervous system disorders such as Psychosis, Parkinson’s and Alzheimer’s disease. In spite of several advantages, the intra- nasal route faces many challenges. Hence, a complete understanding of every aspect re- lated to nose to brain delivery is of utmost importance. This article reviews the mecha- nism of nose to brain drug transport, challenges and approaches for nose to brain drug delivery, a few specialized olfactory delivery devices and some applications of this novel route of brain targeting. Keywords: Bioavailability, blood brain barrier, central nervous system, devices, nose to brain, olfactory pathway. 1. INTRODUCTION Central nervous system (CNS) disorders are one of the leading causes of disability requiring more extended care and hospitalizations than most other diseases. It has been estimated that around 10 million people in the world are living with Parkinson’s disease and the number of CNS re- lated disorders is predicted to rise to about 1.9 bil- lion by 2020 if their curative treatments are not found. The cause of most of the CNS disorders is still a mystery. Treating CNS diseases such as Parkinson’s disease, Alzheimer’s disease, Schizo- phrenia, Stroke, Epilepsy, Brain tumor is extremely *Address correspondence to this author at the Department of Phar- maceutics, Vivekanand Education Society’s College of Pharmacy, Hashu Advani Memorial Complex, Behind Collector Colony, Chembur (E), Mumbai -400074, Maharashtra, India; Tel: 9769244623; Fax: 022- 25543925; E-mail: rajashree.hirlekar@ves.ac.in difficult due to the presence of various barriers mainly the blood brain barrier (BBB) which re- strict the passage of drug for delivery into the brain. Drugs administered via oral and intravenous route encounters the BBB thereby making the treatment of CNS disorders very challenging. Sci- entists are therefore investigating a suitable drug delivery system which could allow the drug to by- pass the barriers and enter the brain for the man- agement of brain diseases [1-5]. Nasal drug delivery has been in use for topical application of drugs intended for local action for a very long time. The Ayurvedic system of Indian medicines also recognizes nasal therapy (Nasya karma) as a form of treatment. In the early 1980s, the nasal route was introduced as a promising al- ternative to other conventional drug delivery route for systemic effect. The intranasal route has now A R T I C L E H I S T O R Y Received: October 22, 2016 Revised: May 31, 2017 Accepted: July 27, 2017 DOI: 10.2174/1574885512666170921145204 2212-3903/18 $58.00+.00 ©2018 Bentham Science Publishers