New Pharmacological Agents to Aid Smoking Cessation and Tobacco Harm Reduction: What has been Investigated and What is in the Pipeline?

A wide range of support is available to help smokers to quit and aid attempts at harm reduction, including three first-line smoking cessation medications: nicotine replacement therapy, varenicline and bupropion. Despite the efficacy of these, there is a continual need to diversify the range of medications so that the needs of tobacco users are met. This paper compares the first-line smoking cessation medications to: 1) two variants of these existing products: new galenic formulations of varenicline and novel nicotine delivery devices; and 2) twenty-four alternative products: cytisine (novel outside of central and eastern Europe), nortriptyline, other tricyclic antidepressants, electronic cigarettes, clonidine (an anxiolytic), other anxiolytics (e.g. buspirone), selective 5-hydroxytryptamine (5-HT) reuptake inhibitors, supplements (e.g. St John’s wort), silver acetate, nicobrevin, modafinil, venlafaxine, monoamine oxidase inhibitors (MAOI), opioid antagonist, nicotinic acetylcholine receptors (nAChR) antagonists, glucose tablets, selective cannabinoid type 1 receptor antagonists, nicotine vaccines, drugs that affect gamma-aminobutyric acid (GABA) transmission, drugs that affect N-methyl-D-aspartate receptors (NMDA), dopamine agonists (e.g. levodopa), pioglitazone (Actos; OMS405), noradrenaline reuptake inhibitors, and the weight management drug lorcaserin. Six criteria are used: relative efficacy, relative safety, relative cost, relative use (overall impact of effective medication use), relative scope (ability to serve new groups of patients), and relative ease of use (ESCUSE). Many of these products are in the early stages of clinical trials, however, cytisine looks most promising in having established efficacy and safety and being of low cost. Electronic cigarettes have become very popular, appear to be efficacious and are safer than smoking, but issues of continued dependence and possible harms need to be considered

Drug delivery from structured porous inorganic materials

Structured porous inorganic materials show high chemical and mechanical stability under an array of physiological conditions. Their hydrophilic character and porous structure can in principle be tailored to control the diffusion rate of an adsorbed or encapsulated drug, gene, or protein. This organized porosity has been used to achieve a sustained, controlled, or pulsed release in drug delivery applications. Their large surface areas together with their large pore volumes have been used to improve the solubility of poorly soluble drugs. Their low density allows them to float in the gastrointestinal tract and prolong the gastric retention of oral drugs. In addition, their easy surface functionalization allows their grafting with bioadhesive and targeting moieties, and their interior pore volume protects biological payloads from physiological degradation. Some of those porous inorganic materials can be synthesized or microfabricated to form deposits thus acting as drug reservoirs. Finally, diffusion-controlling porous membranes or coatings of those materials can be tailored with specific pore sizes to control drug release in eluting devices. Current research is focused on designing on demand targeted drug delivery systems using those inorganic porous materials as reservoirs together with triggering systems on their pore entrances to be externally activated to release the encapsulated therapeutic moiety. All of the previous scenarios will be overviewed to demonstrate the numerous possibilities of structured porous inorganic materials in drug delivery applications.Financial supports from the 2006 Ramón y Cajal program and the Fundación Ramón Areces are gratefully acknowledged.Peer reviewe