In-dwelling microfluidic device for precise and reliable intranasal drug delivery during freely-moving behavior

Abstract

Many substances/drugs are administered intranasally (IN). These include opioid overdose reversal drugs, anti-epileptic medications, migraine medications, hormone treatments, and medicines to treat/prevent allergies, colds, and flues including nasally-administered vaccines, corticosteroids, antihistamines, and decongestants. Additionally, IN administration is the preferred route of entry by users of illicit drugs. Despite the widespread use of the IN route of administration, there is no established paradigm to access this route of administration preclinically to yield precise and reliable control over delivery. This poses major gaps in therapeutic discovery/testing, establishing pharmacokinetic/pharmacodynamic relationships of therapeutics, and understanding the mechanisms of actions of therapeutics. We developed an in-dwelling microfluidic device, that, when implanted upon the nasal bone, accesses the nasal cavity to allow reliable and precise IN fluid delivery during freely-moving behavior. We validated this device, called the Nasal Access Port (NAP), to confirm it allows rapid and precise control of fluids. We further exemplified the application of the NAP for studying outcomes of IN cocaine in mice, including its pharmacokinetic profile, and both the rapid release of dopamine (DA) and behavioral effects upon IN cocaine. By achieving precise and reliable access to the IN route of administration, the NAP represents a significant methodological advance with broad applicability in the biomedical and life sciences, especially in the neuroscience, pharmacology, medicinal chemistry, and physiology domains.