title: Niosomal encapsulation of the antitubercular drug, pyrazinamide.
abstract: 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.
authors.affiliation: Pharmaceutical Technology Department, National Research Centre (NRC), Dokki, Cairo, Egypt. dr_elridy@yahoo.com
authors.forename: Mohammed Shafik
authors.initials: MS
authors.lastname: El-Ridy
authors.forename: Ahmed
authors.initials: A
authors.lastname: Abdelbary
authors.forename: Essam Amin
authors.initials: EA
authors.lastname: Nasr
authors.forename: Rawia Mohammed
authors.initials: RM
authors.lastname: Khalil
authors.forename: Dina Mahmoud
authors.initials: DM
authors.lastname: Mostafa
authors.forename: Ahmed Ibrahim
authors.initials: AI
authors.lastname: El-Batal
authors.forename: Sameh Hosam
authors.initials: SH
authors.lastname: Abd El-Alim
mesh_terms: D000818:Animals; D000995:Antitubercular Agents / Q000008:administration & dosage*; D004337:Drug Carriers; D005260:Female; D006168:Guinea Pigs; D006863:Hydrogen-Ion Concentration; D008081:Liposomes; D008297:Male; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D010316:Particle Size; D011718:Pyrazinamide / Q000008:administration & dosage*; D013223:Statistics as Topic; D014376:Tuberculosis / Q000188:drug therapy*
chemical_list: D000995:Antitubercular Agents; D004337:Drug Carriers; D008081:Liposomes; D011718:Pyrazinamide