J Pharm Pharmaceut Sci (www.cspsCanada.org) 12(3) 288 - 311, 2009 288 Intranasal Drug Delivery: How, Why and What for? Anaísa Pires 1,2 , Ana Fortuna 1,2 , Gilberto Alves 2,3 and Amílcar Falcão 1,2 1 Pharmacology Department, Faculty of Pharmacy, University of Coimbra, Coimbra, Portugal. 2 Centre for Neurosciences and Cell Biology, University of Coimbra, Coimbra, Portugal. 3 Health Sciences Research Centre (CICS), Faculty of Health Sciences, University of Beira Interior, Covilhã, Portugal. Received, May 4, 2009, Revised, September 17, 2009; Accepted, October 7, 2009, Published, October 8, 2009. ABSTRACT Over the recent decades the interest in intranasal delivery as a non-invasive route for drugs is increased. Since the nasal mucosa offers numerous benefits as a target tissue for drug delivery, a wide variety of therapeutic compounds may be administered intranasally for topic, systemic and central nervous system action. We have, herein, outlined the relevant aspects of nasal anatomy, physiology and histology, and the biological, physicochemical and pharmaceutical factors that must be considered during the process of discovery and development of nasal drugs as well as in their incorporation into appropriate nasal pharmaceutical formulations. _______________________________________________________________________________________ 1. INTRODUCTION Oral drug delivery is the most desirable route for drug administration whenever systemic effects are intended. Therefore, it is not surprising that the prediction of human oral bioavailability of new drug candidates is currently targeted from the earliest stages of drug discovery and development programmes (1, 2). However, although the oral route remains the most popular for systemic drug administration, low oral bioavailability of some compounds has prompted the search of more effective routes for their systemic delivery (3). Intranasal drug delivery is now recognized to be a useful and reliable alternative to oral and parenteral routes. Undoubtedly, the intranasal administration of medicines for the symptomatic relief and prevention or treatment of topical nasal conditions has been widely used for a long period of time. However, recently, the nasal mucosa has seriously emerged as a therapeutically viable route for the systemic drug delivery. In general, among the primary targets for intranasal administration are pharmacologically active compounds with poor stability in gastrointestinal fluids, poor intestinal absorption and/or extensive hepatic first-pass elimination, such as peptides, proteins and polar drugs (4). The nasal delivery seems to be a favourable way to circumvent the obstacles for blood-brain barrier (BBB) allowing the direct drug delivery in the biophase of central nervous system (CNS)-active compounds. It has also been considered to the administration of vaccines (5-8). The widespread interest in intranasal route for therapeutic purposes other than the topically nasal drug delivery arises from the particular anatomical, physiological and histological characteristics of the nasal cavity, which provides potential for rapid systemic drug absorption and quick onset of action. In addition, intranasal absorption avoids the gastrointestinal and hepatic presystemic metabolism, enhancing drug bioavailability in comparison with that obtained after gastrointestinal absorption (9, 10). On the other hand, intranasal administration also offers several practical advantages either from the viewpoint of patients (non-invasiveness, essentially painless, ease drug delivery and favourable tolerability profile) or pharmaceutical industry (unnecessary sterilization of nasal preparations) (11, 12). Hence, bearing in mind the intrinsic value of intranasal route to overcome patient compliance concerns together with its pharmacokinetic advantages, it appears to be an appropriate route for the treatment of not only acute or chronic nasal diseases, but also for a range of acute or chronic conditions requiring considerable systemic drug exposure (4, 12). ________________________________________ Corresponding Author: Amílcar Falcão, PharmD, Ph.D, Pharmacology Department, Faculty of Pharmacy, University of Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal, Email: acfalcao@ff.uc.pt