Current Drug Discovery Technologies - Volume 6, Issue 3, 2009

Cigarette smoking is the primary cause of lung cancer, cardiovascular diseases, reproductive disorders and delayed wound healing all over the world; as such, the goals of smoking cessation are both to reduce health risks and to improve quality of life. The development of novel and more effective medications for smoking cessation is crucial in the treatment of nicotine dependence. Currently, first-line smoking cessation therapies include nicotine replacement products and bupropion. The partial nicotinic receptor agonist, varenicline, has recently been approved by the FDA for smoking cessation. A newer product seeking approval by the FDA is nicotine vaccine. Clonidine and nortriptyline have demonstrated some efficacy, but side effects may limit their use to second-line treatment products. Other therapeutic drugs that are under development include rimonabant, mecamylamine, monoamine oxidase inhibitors, and dopamine D3 receptor antagonists. In order to increase the range of drugs available for transdermal delivery a number of chemical and physical enhancement techniques have been developed in an attempt to compromise skin barrier function in a reversible manner without concomitant skin irritation. The controlled delivery afforded by constant current iontophoresis, which involves the application of a small electrical potential sets it apart from other technologies. The amount of compound delivered is directly proportional to the quantity of charge passed; it depends on the applied current, the duration of current application and the area of the skin surface in contact with the active electrode compartment. For these reasons, iontophoresis will provide smokers with an additional option to assist in achieving smoking cessation.

Previous studies show that acetylsalicylic acid (aspirin) at low concentrations affects yeast sexual structure development in a similar fashion than oxygen depletion. This is ascribed to its anti-mitochondrial action. In this study, we report the same for other anti-inflammatory (i.e. ibuprofen, indomethacin, salicylic acid, benzoic acid) as well as anticancer (Lonidamine) drugs, also known for inhibiting mitochondrial activity in mammalian cells. This is shown by a unique yeast bio-assay, with the mitochondrion-dependent sexual structure, riboflavin production, and hyphal morphology of the yeast Eremothecium ashbyi serving as indicators. These drugs affect this yeast in a similar way as found under oxygen limitation conditions by inhibiting sexual structure development (most sensitive), riboflavin production, and yielding characteristically wrinkled and granular hyphae, presenting a unique “anoxic” morphological pattern for this yeast. Only drugs associated with anti-mitochondrial activity presented such a pattern. This bio-assay may find application in the screening for novel drugs from various sources with anti-mitochondrial actions.

Curcumin, a polyphenolic compound derived from the dietary spice turmeric, possesses diverse pharmacologic effects including anti-inflammatory, anti-oxidant, anti-proliferative and anti-angiogenic activities. Accumulating experimental evidence suggests that curcumin interferes with a variety of molecular targets and processes involved in cancer. Further, data obtained in multiple preclinical models, as well as in preliminary clinical trials, have documented minimal toxicity of curcumin, even at relatively high doses. However, the clinical advancement of this promising molecule has been hindered by its poor water solubility, short biological half-life, and low bioavailability after oral administration. A variety of approaches are being pursued to overcome these limitations, which include synthesis of curcumin analogues, the use of adjuvants (e.g. piperine), and the development of improved delivery platforms for the parental compound, including liposomal, nanoparticulated and phospholipid complex formulations of curcumin. This review is intended to provide the reader an update on the bioavailability and pharmacokinetic pitfalls of free curcumin, and a comprehensive cataloging of ongoing approaches that have been undertaken to resolve these issues, with the goal of harnessing the true potential of this anti-cancer agent in the clinical arena.

Insulin remains a key to the management of diabetes. The early addition of insulin to oral therapy in type-2 patients is recognized as an effective option that can help improve glycemic control and reduces the complications and contribute to more favorable outcomes. Controlling blood glucose levels within acceptable limits is crucial to the long-term health of patients with diabetes. The benefits of patient education and chronic disease management tools cannot be underestimated as many patients will require education and help in initiation of insulin therapy to achieve glycemic targets. The wide choice of insulin formulations and the ever-expanding range of delivery methods are now available. These methods made insulin administration easier, less painful, more discreet, and more accurate than ever before thus providing important tools to overcome barriers to insulin initiation and improve achievement of glycemic goals. In addition, exciting developments in newer therapeutics have increased the potential for optimal glycemic control. This review discusses how these approaches can help patients manage their diabetes effectively by considering new insulin formulations and delivery devices and newer therapeutics.

Supercritical fluid chromatography (SFC) is a fully mature technique and can readily be coupled to mass spectrometers relatively easily. In the last years, supercritical fluid chromatography coupled with mass spectrometry (SFCMS) has had a great advance in productivity, due to increase in reliability and robustness of both SFC and MS systems, the need to push drug discovery faster, and as a potential solution to old problems unsolved and new problems yet to be encountered. This article will illustrate the role of SFC-MS analysis in drug discovery process.