 |
Next Safety’s Nicotine Replacement and Cessation Device |
Next Safety has demonstrated that its pulmonary delivery device delivers nicotine with higher efficacy than cigarettes. Next Safety’s approach currently delivers more than 80% of the nicotine present in its device into the blood stream. Advanced optical characterization techniques performed by a third party laboratory showed that 99.8% of the nicotine droplets created in Next Safety’s pulmonary drug delivery device were between one and three microns in diameter and therefore immediately respirable through the alveoli of the lungs.
Nicotine and Tobacco
Nicotine (C10H14N2) is a basic, colorless to pale yellow, hygroscopic, oily, volatile liquid that has an unpleasant pungent aroma and a sharp, burning, persistent taste. It is an alkaloid and in plants is found most abundantly in tobacco, constituting 0.3-5.0% of the tobacco plant by dry weight.
At nontoxic levels, nicotine has numerous psychoactive and physiologic effects which are perceived by users as beneficial. With respect to the central nervous system (CNS), nicotine increases dopamine, acetylcholine, norepinephrine and beta-endorphin levels creating a sense of enhanced pleasure, decreased anxiety, alert relaxation and enhanced memory. Nicotine is also an appetite suppressant, which is considered beneficial by many users. It is not surprising then that nicotine is highly addictive. Several studies have shown it to be more addictive than cocaine or heroin.
Smoking tobacco is by far the most common method used for nicotine delivery. While nicotine itself can be toxic at high levels, the adverse health issues associated with smoking are caused by the other 4000-plus products of combustion within tobacco smoke. Products of tobacco combustion are divided into visible components, also known as “tar,” and non-visible components.
Tar is a resinous mix of partially combusted particulate matter. Upon combustion of tobacco, nicotine is vaporized and attaches to tar particles, which are inhaled by the smoker. The tar transports the nicotine vapor into the deep lungs where it is quickly absorbed at the alveolar level into the pulmonary blood stream. Tar accumulates in a smoker’s lung tissue over time and is the most destructive component within tobacco smoke. For example, tar contains polycyclic aromatic hydrocarbons (like benzopyrene) which are proven mutagens and carcinogens. The non-visible component of tobacco smoke also contains numerous harmful compounds such as carbon monoxide, carbon dioxide, nitrogen oxides and ammonia.
Negative Health Effects of Tobacco Exposure
The adverse health care consequences of smoking tobacco are enormous and incontrovertible. According to the WHO, tobacco is the second major cause of death in the world, currently accounting for one in ten deaths worldwide (5 million each year). Of the 650 million current smokers in the world today, half of these of will die from tobacco-related illness. Tobacco is the single largest preventable cause of disease and premature death. It is the primary risk factor in heart disease, stroke and chronic lung disease. In addition, it has been linked to numerous cancers, including lung, laryngeal, esophageal, mouth, bladder, cervical, pancreatic and kidney cancer. In China, for example, smoking will contribute to the death of one third of all young Chinese males (under 30 years old) currently alive. In the United States, the 1999 National Health Interview Survey estimated that 46.5 million adults smoke and that 440,000 die each year from smoking related causes. In men, smoking is estimated to decrease life expectancy by 13.2 years and in women by 14.5 years.
There are also tremendous health-related costs associated with smoking. In the United States, it is estimated that smoking-related direct medical costs total $75 billion/year, and another $82 billion/year is lost from decreased productivity. This totals $157 billion/year spent or lost dealing with smoking-related illnesses.
Furthermore, it is now understood that cigarette smoke is not only harmful to the smoker, but also can affect the health of non-smokers when they passively inhale the smoke of other peoples’ cigarettes (otherwise known as environmental or secondhand smoke). In adults, secondhand smoke is a risk factor for numerous types of cancer (including lung and breast cancer), heart disease, lung disease and many others. Passive smoke exposure also increases the risk of disease in children and infants.
Nicotine Replacement Therapy and Smoking Cessation
There are several FDA approved nicotine replacement treatments (NRTs) available both over-the-counter and as a prescription for use in smoking cessation programs. These include:
- Nicotine Gum- FDA approved. Available over the counter. Available in 2mg and 4 mg dosages. Absorption occurs across the buccal mucosa.
- Nicotine Patches- FDA approved. Available over the counter and as a prescription. Available in 21mg, 14 mg and 7 mg/24 hours and 15 mg/16 hours. Absorption occurs transdermally.
- Nicotine Inhaler- FDA approved. Prescription only. Each cartridge delivers 4 mg of nicotine. Absorption occurs across the buccal and oropharyngeal mucosa.
- Nicotine Nasal Spray- FDA approved. Prescription only. One dose equals a .5 mg spray to each nostril (1 mg total per dose). Absorption occurs across the nasal mucosa.
- Nicotine Polacrilex Lozenge- FDA approved. Available over the counter. Available in 2 mg and 4 mg pieces. Absorption occurs across the buccal mucosa.
Other NRTs available in countries outside of the United States (not FDA approved) include sublingual tablets, nicotine water and nicotine lollipops.
None of these systems deliver significant amounts of nicotine to the alveolar level of the lungs. Instead, they rely on the absorption of nicotine across the skin or across the nasal, buccal, or oropharyngeal mucosa. As a result, absorption is much slower and much less efficient than that typical of smoking. This leads to slower and much lower peak nicotine concentrations compared to those produced by cigarettes. Of the currently available NRT listed above, the nicotine inhaler is purported to have delivery characteristics most like cigarettes. However, Lunell et al confirmed that absorption occurs primarily across the buccal mucosa (not the lungs), and that the arterial nicotine concentration spike, typical of cigarette smoking, does not occur with the inhaler.
The peak serum levels achieved with the currently available NRTs may be adequate to ameliorate or prevent withdrawal symptoms. However, they do little to satisfy the acute craving for the “buzz” created by the rapid onset, high peak serum nicotine levels typical of tobacco smoke. This may be the main reason why so few people that use NRT in attempts to quit smoking have long-term success. They simply give in to these persistent cravings, which currently can only be satisfied through smoking.
The Appeal and Rationale for Alternative Nicotine Delivery Systems
Even though the adverse health effects of smoking are well understood and increasingly publicized (especially in developed nations), smoking remains very prevalent. According to the WHO, 650 million people in the world today smoke cigarettes. Fifteen billion cigarettes are sold daily (10 million every minute). Most of these smokers are located in east Asia and the Pacific regions. In China alone, there are 300 million smokers, more than the entire US population. It is estimated that Chinese smokers consume 1.7 trillion cigarettes per year (or 3 million cigarettes per minute).3 In general, smoking prevalence is increasing in the developing world and falling in developed nations. However, even in the most “developed” nations, where public awareness of the adverse health effects of smoking are well known, a significant portion of the population continues to smoke. For example, 20.9% of all adults in the United States (45.1 million people) smoke cigarettes.
Given the enormity of the personal and public health problems caused by smoking, it is agreed upon by all physicians and public health care organizations (including the CDC and WHO) that the best thing that smokers can do is to quit. However, even with the wide availability of NRTs and newer non-nicotine drugs (varenicline, bupropion, etc.), long term success is seen only in 3-7% of the general population.
Again, it is important to emphasize that all of the chronic adverse health effects caused by nicotine addiction currently come from the use of tobacco (most notably smoking) as a delivery device (not the nicotine itself). Thus, even though many smokers recognize the ill-effects of tobacco exposure and want to stop, their addiction to nicotine as delivered by the inhalation of tobacco smoke, prevents them from quitting since there are currently no true alternatives. It stands to reason that a safe, effective, long-term alternative nicotine delivery system capable of providing nicotine to the user in a way analogous to tobacco smoke would have great appeal to these individuals. In addition, as such a platform becomes more popular, it would have the potential of significantly reducing the aggregate impact of smoking-related diseases on a global scale.