Development and characterization of a transdermal patch and an emulgel containing kanamycin intended to be used in the treatment of mycetoma caused by Actinomadura madurae.

BACKGROUND: Mycetoma is a chronic, degenerative, and incapacitating infection of the skin and subcutaneous tissue. AIM: This study focuses on developing a kanamycin-based auxiliary system intended to be used in the treatment of mycetoma caused by Actinomadura madurae. METHODS: Transdermal patches (with two different formulations: one with free kanamycin [K] and the other one with kanamycin adsorbed in silica [K-SG]) and an emulgel were developed. Both patches were prepared by the casting-evaporation technique. To characterize them, differential scanning calorimetry, bioadhesion, post-moisture detachment, strength and rupture distance, gas exchange, water uptake, and dissolution studies were carried out. The emulgel (containing 0.57% of kanamycin) was prepared from an oil-in-water emulsion, which was then incorporated to a gel. RESULTS: the patches with the best characteristics contained 22.9% of silica and 14.6% of kanamycin. Dissolution studies indicated that 8.8% of kanamycin released from K and 3.2% from K-SG at 24h. The emulgel containing 0.57% of kanamycin showed good technological characteristics for its application to the skin (viscosity, 44.9 +/- 1.4 poises; pH, 6.9 +/- 0.4; and penetrability, 52.7 +/- 5.1). CONCLUSIONS: The optimal patches were those containing 15.9% of freely dispersed kanamycin (K) and 14.6% of kanamycin adsorbed in silica (K-SG), which corresponds to the batch 2-0.8. The assessments performed to both pharmaceutical forms (patches and emulgel) show that they have the adequate technological characteristics for being used as an auxiliary in the treatment of actinomycetoma caused by A. madurae.

The use of iontophoresis in the administration of nicotine and new non-nicotine drugs through the skin for smoking cessation.

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.

Preparation of nanoparticles by solvent displacement using a novel recirculation system.

Submicron colloidal suspensions of poly(epsilon-caprolactone) (PCL) were prepared by the solvent displacement method, using either the conventional form or a new recirculation device. In the latter case, a process that allows the recirculation of the aqueous phase into a device, providing a continuous flow, is proposed. The influence of the organic solution injection rate and polymer concentration on mean particle size and process yield were studied for both methods. The recirculation rate was also analyzed for the recirculation system. Nanoparticles (NPs) showed mean sizes that ranged from 156 to 381. The smallest particles were obtained when recirculation rate, injection rate and polymer concentration were maximized but at the expense of the yield. The only acceptable yields (83-96%) were obtained at the lowest PCL concentration (2.5% w/v). ANOVA tests (alpha = 0.05) showed that the variables implicated in the recirculation system significantly affected the mean particle size and the process yield. The entrapment efficiencies of NPs prepared by the conventional method were not significantly different (alpha = 0.05) from those obtained by the recirculation system.

Chemical enhancers for the absorption of substances through the skin: Laurocapram and its derivatives.

Absorption enhancers are substances used for temporarily increasing a membrane's permeability (e.g., the skin and mucosa), either by interacting with its components (lipids or proteins) or by increasing the membrane/vehicle partition coefficient. This article presents the results of biophysical and permeability studies performed with Laurocapram and its analogues. As shown, Laurocapram and its analogues present different enhancing efficacies, for most of both hydrophilic and lipophilic substances. The enhancing effect of Laurocapram (Azone) is attributed to different mechanisms, such as insertion of its dodecyl group into the intercellular lipidic bilayer, increase of the motion of the alkylic chains of lipids, and fluidization of the hydrophobic regions of the lamellate structure. Toxicological studies reveal a low toxicity for Laurocapram, and for some derivatives, a relationship exists between toxicity and the number of carbons in the alkylic chain. Very important, when applied to human skin, Laurocapram shows a minimal absorption, being quickly eliminated from circulation. However, although Laurocapram and its derivatives have been shown to provide enhancement, they have not been widely accepted because of their suspected pharmacological activity or questions about their safety.