Patel. European Journal of Pharmaceutical and Medical Research www.ejpmr.com 281 INTRANASAL ROUTE FOR CNS DELIVERY: OVERVIEW AND RECENT ADVANCEMENTS Jignesh Patel* *Formulation Development Department, QS Pharma, Boothwyn, PA. Article Received on 13/04/2017 Article Revised on 04/05/2017 Article Accepted on 25/05/2017 1 INTRODUCTION Drug delivery to the brain has been difficult to achieve due to the presence of the blood-brain barrier, which is formed by tight junctions within the capillary endothelium of the vertebrate brain. Drugs used against CNS diseases should reach the brain by crossing the BBB. The tight junctures between endothelial cells in brain results in a very high trans-endothelial electric resistance of 1500-2000 W cm 2 compared to 3-33 W cm 2 of other tissues like skin, bladder, colon, lung etc. which significantly affects uptake of drugs by brain. [1,2] However, certain classes of drugs like benzodiazepines such as diazepam, due to its high lipophilicity, readily cross the BBB but the passage of hydrophilic drugs and macromolecules like protein and peptide through BBB is quite difficult. A great deal of efforts, therefore, has been undertaken in developing ways to open, defeat or circumvent the BBB in order to deliver drugs from blood to brain. In recent times, intranasal delivery is explored for its potential to deliver the drugs to CNS. In addition to absorption through respiratory region, the finding of potential of olfactory region to deliver the drugs bypassing the BBB has shown a great potential. However, the enzymatic degradation in the nasal cavity, short residence time, and resistance imparted by mucus are some of the challenges to overcome for effective intranasal delivery. This review takes a look at the basics of intranasal delivery to deliver therapeutic agents to brain, and some of the published work in the field, challenges against optimum delivery and approaches to overcome them. 2 INTRANASAL DRUG DELIVERY FOR CNS DELIVERY Feeling pleasure on sniffing cocaine and sense of smell with odorants give an idea that there should be some relation between nose and brain. Following this earlier rudimentary finding, the nasal route for the delivery of the CNS drugs to the brain has been widely studied over the last one and half decades. [3,4] In the recent years, the nasal route has been exploited for the systemic delivery of polar drugs, peptides and proteins as well. [5, 6] Many of such drugs are ineffective during oral administration mainly because of first pass metabolism and enzymatic degradation in the gastrointestinal tract, but can be absorbed nasally due its avoidance of the aforementioned problems. Nasal route of drug delivery to CNS also offers several advantages over the other alternative routes. Due to rapid absorption and higher bioavailability in CNS, the dose required for administration is lower than that required in systemic circulation and there is a faster onset of action as compared to oral administration. It is also a non-invasive, painless, and easily administered, does not require the formulation to be sterile, and increases patient comfort, convenience and compliance. [7] The risk of overdose is also reduced because the maximum volume deliverable in the nose is not more than 300μl. [8, 9] 2.1 Nasal anatomy and physiology The human nasal cavity can be divided into two halves by a nasal septum. Each of the nasal cavities can be subdivided into three regions: the olfactory region, the SJIF Impact Factor 4.161 Review Article ISSN 2394-3211 EJPMR EUROPEAN JOURNAL OF PHARMACEUTICAL AND MEDICAL RESEARCH www.ejpmr.com ejpmr, 2017,4(06), 281-292 *Corresponding Author: Jignesh Patel Formulation Development Department, QS Pharma, Boothwyn, PA. ABSTRACT This review focuses on the researchers’ efforts to explore intranasal route to deliver drugs to CNS. With a brief overview of nasal anatomy, article discusses various possible mechanism through which drugs could be delivered to brain via intranasal route. Physiochemical properties of drugs affecting nasal absorption and role of formulations in brain delivery through intranasal route are discussed. Despite of the potential of nasal route to deliver the drugs to brain, enzymatic activity in nasal cavity, short residence time and higher mucociliary clearance are some of the short-comings and various approaches to overcome these short-comings are discussed. Additional focus on enhancement techniques to deliver proteins and peptides is given. In the final part of the article, some of the recent studies of intranasal delivery to brain for small molecules, protein and peptide are discussed. KEYWORDS: Intranasal drug delivery, CNS delivery, olfactory pathway, nasal mucosa, protein and peptide delivery, permeation enhancers.