Lead by the Nose

When considering drug delivery, the oral and injectable routes are perhaps the most well used and well discussed, but many interesting advances are being seen in the nasal drug delivery field that should not be overlooked. The main advantages associated with the nasal route are ease of use, direct access into the bloodstream, rapid onset of action, and avoidance of hepatic first-pass metabolism, to name just a few. The nasal mucosa’s proximity to the brain has also fuelled much interest in potentially using the nasal route to deliver drugs to the brain, although in practice this has proved challenging.

Despite the benefits of the nasal route, it is not well used for commercial pharma products. One of the reasons is perhaps the complexity of development – developing a new drug molecule is challenging enough, and using the nasal route also requires the design of an effective and patient-centric delivery device. Different studies have demonstrated that the device plays an important role in drug efficacy, as well as market success, and, overall, nasal drug delivery devices are well established and accepted by patients. A good device should be easy to use for everyone – healthcare professionals and patients. The device-user interface is a key element of the device development and human factor studies are crucial to ensure a device is intuitive and comfortable to use. Advances in devices and electronics are also opening up the possibility of adding features to increase patient safety and adherence, such as a “do not forget me” function.

With increasing competition in the pharma market today, the nasal cavity is worth exploring to differentiate drugs, or to refresh existing drugs with a new delivery method. On the locally-acting drugs side, several corticosteroid nasal drugs have recently (or will soon) come off patent, providing opportunities for generics companies. Vaccines are another good application for nasal sprays; for example, MedImmune’s FluMist is sprayed into the nose to help protect against influenza. One of the most popular indications for nasal drug delivery, however, is pain management, and a number of approved medicines are already on the market, such as the Sumatriptan nasal spray for treating migraine headaches. In recent years, nasal drug delivery devices have improved their capabilities to target anatomical regions of interest for improving drug efficacy and pain relief. For instance, Optinose has developed an innovative concept for nasal aerosol delivery, using mouth exhalation to protect the lungs against particle penetration. Performance of nebulizer systems has also improved with mesh technology to target sinuses and chronic rhinosinusitis patients.

I see no reason why the nasal route shouldn’t see increased future use in hospital treatments, such as following an operation, breakthrough pain associated with cancer, or multiple sclerosis. In fact, more and more nasal sprays are being developed for emergency use because of their fast absorption and onset of action; for example, nasal sprays have been developed for treating opioid overdose, anaphylaxis, and cardiac arrest.

One intriguing area of development is the delivery of drugs into the brain via the nasal cavity to treat central nervous system conditions. Nose-to-brain drug delivery has seen significant research during the last decade, but no real nose-to-brain proof of concept for humans has been realized. Many studies in animals claim direct nose-to-brain transport along the olfactory and trigeminal nerves, but the animal olfactory zone is more developed and does not prove human efficiency. Some clinical trials in man have suggested the potential of reaching the brain through nasal drug delivery, but definitive proof is lacking. However, this is a vibrant area of fascinating research, particularly for Alzheimer’s and Parkinson’s.

Despite the challenges, I am confident that the industry will see more nasal sprays reaching the market in the future. Nasal delivery is a fascinating area full of potential. Some of the projects I have noted recently include clinical research on intranasal octreotide to treat acromegaly and neuroendocrine tumors (1); using shark antibodies to cross the blood-brain barrier (2); and nose to brain drug delivery of Oxytocin in autism patients (3). Those with a nose for new drug development opportunities should not ignore the nasal route!