ABSTRACT
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.
Subject(s)
Antitubercular Agents/administration & dosage , Drug Delivery Systems , Ethambutol/administration & dosage , Lung/metabolism , Animals , Antitubercular Agents/pharmacokinetics , Antitubercular Agents/toxicity , Chemistry, Pharmaceutical , Delayed-Action Preparations , Drug Stability , Ethambutol/pharmacokinetics , Ethambutol/toxicity , Guinea Pigs , Liposomes , Mice , Time Factors , Tissue DistributionABSTRACT
Nonionic surfactant (NIS) vesicles (niosomes) formed from self-assembly of hydrated synthetic NIS monomers are capable of entrapping a variety of drugs and have been evaluated as an alternative to liposomes. Nystatin (NYS) is a polyene antifungal drug that has been used in the treatment of cutaneous, vaginal and oral fungal infections since the 1950s. The aim of this work is to encapsulate NYS in niosomes to obtain a safe and effective formula administered parenterally for neutropenic patients. NYS niosomes were prepared by the thin-film hydration method using Span 60 or Span 40 and cholesterol (CHOL). Stearylamine and dicetyl phosphate were added as the positive and negative charge-inducing agents (CIA), respectively. Two molar ratios were used, namely NIS/CHOL/CIA (1:1:0.1 and 2:1:0.25). Neutral and positively charged niosomes gave the highest encapsulation efficiencies. NYS niosomes were characterized using transmission electron microscopy, differential scanning calorimetry and dynamic light scattering. The release of neutral and negatively charged NYS niosomes was estimated, and it showed a slow sustained release profile. A 25-kGy γ-irradiation dose was sufficient to sterilize the investigated vesicles. NYS niosomes exerted less nephrotoxicity and hepatotoxicity in vivo, showed higher level of drug in vital organs and revealed pronounced efficacy in elimination of the fungal burden in experimental animals infected with Candida albicans compared with those treated with free NYS. Niosomal encapsulation thus provided means for parenteral administration of NYS, reducing its toxicity and making it a more active antifungal agent.
Subject(s)
Antifungal Agents/administration & dosage , Candidiasis/drug therapy , Drug Delivery Systems , Liposomes/administration & dosage , Nystatin/administration & dosage , Analysis of Variance , Animals , Antifungal Agents/chemistry , Antifungal Agents/pharmacology , Disease Models, Animal , Female , Liposomes/chemistry , Liposomes/pharmacology , Male , Mice , Nystatin/chemistry , Nystatin/pharmacology , Random Allocation , Rats , Rats, WistarABSTRACT
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.
