Niosomal encapsulation of ethambutol hydrochloride for increasing its efficacy and safety.

CONTEXT: Tuberculosis (TB) is a worldwide health concern. In 2011, about 8.7 million new cases developed TB and 1.4 million people died from it. OBJECTIVE: Enhancement of ethambutol hydrochloride activity and safety in treatment of TB through niosomal encapsulation. MATERIALS AND METHODS: Niosomes were prepared by the thin-film hydration method. They were characterized, investigated for in vitro release, lung disposition and in vivo biological evaluation. RESULTS: Entrapment efficiency of ethambutol hydrochloride ranged from 12.20% to 25.81%. Zeta potential values inferred stability of neutral and negatively charged formulations. In vitro release was biphasic. Lung targeting was increased by niosomal encapsulation. Biological evaluation revealed superiority of niosomal ethambutol hydrochloride over the free drug. DISCUSSION: Neutral and negatively charged niosomal vesicles are dispersed homogenously unlike positively charged vesicles. Niosomal encapsulation results in controlled drug release. Niosomal formulations targeted more drugs to mice lungs for a prolonged period of time resulting in: decreased root-specific lung weight, bacterial counts in lung homogenates and optimizing pathological effect on guinea pigs lungs, livers and spleens. CONCLUSION: Encapsulation of ethambutol hydrochloride in niosomal formulations for the treatment of TB provides higher efficacy and safety compared with the free drug.

Niosomal encapsulation of the antitubercular drug, pyrazinamide.

It is estimated that more than one-third of the world population is infected with Mycobacterium tuberculosis. Pyrazinamide (PZA) plays a unique role in shortening therapy because it kills a population of semilatent tubercle bacilli residing in an acidic environment. Niosomes are vesicles made up of non-ionic surfactant and exhibit behavior similar to liposomes in vivo. Preparation of PZA niosomes took place using different molar ratios of Span 60 and Span 85, with cholesterol (CH) i.e. Span: CH (1:1) and (4:2). Dicetyl phosphate and stearyl amine were used in preparation of negative and positively charged niosomes, respectively. Free PZA was separated by cooling centrifugation and estimated spectrophotometrically at 268.4 nm. Niosomes were characterized by electron microscopy and differential scanning calorimetry. The highest percentage PZA entrapped was obtained using Span 60 and the molar ratio (4:2:1) negatively charged niosomes. This was followed by the neutral PZA neutral (4:2) Span 60 niosomes. Biological evaluation of selected PZA niosomal formulations took place on guinea pigs infected with M. tuberculosis. The present work is an attempt to target maximum concentration of PZA to the affected site (lungs) and to exclude undesirable side effects and decrease toxicity. Macrophage targeting and overcoming drug resistance is our final goal.