Intranasal Drug Delivery: How, Why and What for ?(Pires J, et.al. 2009) Pharm Pharmaceut Science, 12(3) 288 – 311, 2009
Even though oral administration of drugs are preferred in most cases of drug administration intending a systemic effect, due to reactions of certain compounds alternative routes have been considered. Nasal drug delivery is rapidly emerging as an alternative to oral drug delivery. Compounds such as peptides, proteins and polar drugs which that would give out poor stability in gastrointestinal tact, compounds that needs hepatic first pass elimination, poor absorption could used in nasal delivery. Main important of nasal delivery is its ability to direct transport drugs to the central nervous system (CNS) by manipulation the blood-brain barrier (BBB). Nasal delivery also results in rapid systemic drug absorption and a quick onset of action, it is also non-invasive, painless and shows ease of drug delivery. These major advantages has resulted in nasal delivery for administration of vaccines. There could be drawbacks in certain drugs, which have properties that may alter the physiological and pathological conditions of nasal mucosa resulting in changes in drug absorption and efficiency. Low volumes around 100-150 micro litre would be the amounts that could be administrated due to the restrictions in the nasal cavity.
Main functions of nasal cavity are assisting breathing and olfaction. Nasal cavity also helps in humidifying and heating air before it reaches the lowest air ways. The mucus and hair in the nasal cavity helps trap unwanted particles and pathogens by mucocilary clearance.
Name Location in nasal cavity
The Nasal vestibule the interior part of the nasal cavity, just inside the nostrils, and presents an area about 0.6 cm2 Afford high resistance against toxic environmental substances.
Respiratory region is largest part of the nasal cavity and it is divided in superior, middle and inferior turbinates which are projected from the lateral wall Humidification and temperature regulation of inhaled air. Between them there are spaces, called meatus, which are passageways where airflow is created to assure a close contact of the inhaled air with the respiratory mucosal surface.
The olfactory region is located in the roof of the nasal cavity and extends a short way down the septum and lateral wall. Olfactory one is also pseudostratified but contains specialised olfactory receptor cells important for smell perception. In this area there are also small serous glands (glands of Bowman) producers of secretions acting as a solvent for odorous substances.
The nasal respiratory mucosa, and epithelium constituted by the epithelium, basement membrane and lamina propria. The nasal respiratory epithelium consists of pseudostratified columnar epithelial cells, goblet cells, basal cells and mucous and serous glands Microvilli are important to enhance the respiratory surface area, while cilia are essential to transport the mucus toward the nasopharynx. Under physiological condition, nasal epithelium is covered with a thin mucus layer produced by secretary glands and goblet cells. These ones secrete granules filled with mucin, a glycoprotein that determines the viscosity of the mucus. humidification and warming of the inhaled air, and also offers physical and enzymatic protection.
Intra Nasal drug delivery
Several approaches have been considered for nasal drug delivery depending on the nature of the pathological condition for example in acute or chronic, drug treatment effects such as local, system or at CNS are considered when choosing a mode of drug transportation. Several type of nasal drug delivery is considered.
These types of drug administration are mostly used in cases of topical nasal disorders such as antihistamine and corticosteroids for rhinosinusitis. It is considered as the first option of nasal drug delivery due to its rapid symptom relief and has fewer side effects compared to oral oe parenteral routes. Biofilm bacteria which are resistant to system treatment have been treated recently by using topical antibiotherapy, this method has also helped avoiding systemic toxicity.
Systemic drug delivery is the fastest at present when considering drug delivery. It also has an extended drug absorption compared to intranasal, parenteral and oral forms of drug delivery. There are number of prominent drugs being researched to achieve systemic effect such as morphine, cardiovascular drugs, progesterone insulin, anti-inflammatory agents and anti-viral drugs. Drugs such as zolmitrptan and sumatrpitan used for treatment of migraine and cluster headaches that uses systemic delivery and are already available in the market.
Recently nasal vaccinate against respiratory infection have been investigated as an alternative to classic parenteral route. Nasal vaccines are attempted in enhancing the systemic effect of certain immunoglobulin G and A nasal sections. Nasal vaccine against influenza A and B virus, protosoma- influenza, group B meningococcal native, attenuated respiratory syncytial virus and parainfluenza 3 viruses shows how efficiency of this method.
CNS delivery through nasal route
Due to the isolation and protection of CNS from the outside environment prevent delivery of drugs to the CNS. Tight junction of BBB second line defence mechanisms such as multidrug efflux protein transport reduces the brain exposure also impairs the systemic drug delivery to CNS. Delivery of drugs through olfactory neuroepithelium with or without involvement of paracellular, transcellular, and neuronal transport has been considered as a route of nasal vaccine development. Other routes, such as transportation through trigeminal nerve system of nasal cavity have also been explored.
Factors influencing nasal drug absorption
There are several factors affecting nasal administration. When systemic effect is expected on CNS there are several barriers, such as mucus layer and epithelial membrane, exist before even reaching the blood stream. The transport of drugs may be transcellular where passive diffusion take place between interior of the cells, this is essential for the transportation of lipophilic drugs. Trans-cellular method is mediated by carriers such as organic cation transporters and amino acid transporters in the nasal mucosa. Paracellular mechanism on the other hand transports small polar drugs through adjacent epithelial cells through hydrophilic porous and tight junctions. This transportation method depends on the weight of the drug molecule due to the fact that sizes of tight junctions vary between 3.9- 8.4 mico meters in size. The weight also has an effect on the rate of absorption and extend the absorption. The physiological factors that affect nasal delivery will be discussed in part two of this article.