Drug overdose rates continue to increase, with record numbers tabulated in 2022 (Anon, 2022, Kariisa et al., 2022, Judd et al., 2023a). Overall, there have been over a million deaths tabulated from drug overdose since the turn of the century, and the rates continue to increase yearly with over 110,000 deaths recorded in just 2023 (Anon, 2024a, Anon, 2024b). Opioid overdose initially leads to sedation and hypotension ultimately culminating in respiratory depression and eventually death without intervention (Judd et al., 2023a, Akiba et al., 2023, Kerensky and Walley, 2017). As such, the need for low-cost, effective, easy-to-use, and easily accessible modalities to reverse opioid overdose is of utmost importance (Akiba et al., 2023, Kerensky and Walley, 2017, Judd et al., 2023b, Harris, 2023). The most common form of opioid reversal is naloxone hydrochloride (NHC) which competitively antagonizes opioids and reverses their effects (Kerensky and Walley, 2017, Judd et al., 2023b). First approved by the Food and Drug Administration (FDA) in 1971, naloxone has shown to be a safe way to reverse opioid overdoses and prevent overdose-related deaths (Judd et al., 2023b, Harris, 2023, Fisher and Shafer, 2020).

For the non-medically trained individual, the two types of approved opioid-reversal agents are intranasal spray and an intramuscular autoinjector (Fisher and Shafer, 2020, Cohen et al., 2020). Specifically, naloxone hydrochloride nasal spray is intended for immediate administration as emergency therapy in settings where opioids may be present (Harris, 2023). While in the past opioid-overdose reversal agents were intended for use by health care workers, there is also a desperate need for more access and availability of opioid-reversal agents for use by non-trained bystanders. Prior investigations have shown that naloxone kits are available for non-medical personnel that have some success in the real-world environment (Lim et al., 2016). Yet, its application is limited by concern for poor bioavailability (Strang et al., 2016).

In an effort to make naloxone more widely available, the FDA called for an over the counter (OTC) formulation of naloxone (Fisher and Shafer, 2020, Cohen et al., 2020). To encourage the urgent development of an OTC naloxone, the FDA published a model Drug Facts Label (DFL) for an OTC naloxone product (Cohen et al., 2020). The nasal route allows for rapid absorption and onset of action, high plasma bioavailability, and direct transport to central nervous system from the highly vascularized venous regions of the nasal mucosa to the cardiopulmonary system then quickly to the brain (Hussain et al., 1984). Notably, the theorized level of maximal absorption in the nasal cavity at the level of the inferior turbinate is due to its ability for passive diffusion into the bloodstream (Wermeling, 2013). Further, the intranasal route does not require intravenous access and is easy to use for both non-trained consumers and health care professionals (Sabzghabaee et al., 2014). Recently, the FDA approved two OTC nasal spray formulation of NHC (Harris, 2023, Fisher and Shafer, 2020, Grassin-Delyle et al., 2012, Anon, 2023). In addition, Pocket Naloxone Corp. has developed an OTC naloxone product which is an aqueous isotonic solution of NHC plus common excipients (benzalkonium chloride, edetate disodium, sodium chloride, hydrochloric acid, and citric acid) supplied on a custom-developed nasal swab applicator, known as the PN Naloxone Nasal Swab (PNNNS) (Fig. 1). This nasal swab has been shown in preliminary analysis to be more efficacious (10-fold increased exposure at 2.5 min) than the spray counterpart in prior investigations (Anon, 2022). As such, there is hope that the PNNNS can be a valuable entity in the current fight against opioid overdose.

The efficacy and safety of the PNNNS administered by bystander or non-medical personnel was confirmed in a comparative pharmacokinetic study (PNC 20–001) (McDonald et al., 2018). Of note, exclusion criteria in that study included abnormal nasal anatomy (McDonald et al., 2018). The primary purpose of this investigation was to determine the safety of the nasal swab applicator in a variety of common configurations of nasal anatomy with non-medically trained individuals. These results should re-assure the public that non-medically trained bystanders can safely insert a nasal swab optimized for drug delivery, regardless of the overdosed individual’s sinonasal anatomy due to nasal surgery or other complication.