title: Chemotherapeutic evaluation of alginate nanoparticle-encapsulated azole antifungal and antitubercular drugs against murine tuberculosis.
abstract: The present study was designed to evaluate the chemotherapeutic potential of alginate nanoparticle-encapsulated econazole and antitubercular drugs (ATDs) against murine tuberculosis. Alginate nanoparticles encapsulating econazole and ATDs were prepared by the cation-induced controlled gelification of alginate and were characterized. Drugs were analyzed by high-performance liquid chromatography. All the ATDs were detected above minimum inhibitory concentrations for as long as 15 days and econazole until the day 8 in organs (lungs, liver, and spleen) after administration of encapsulated drugs, whereas free drugs remained detectable for only 12 to 24 hours. Eight doses of alginate nanoparticle-encapsulated econazole or 112 doses of free econazole reduced bacterial burden by more than 90% in the lungs and spleen of mice infected with Mycobacterium tuberculosis. Econazole (free or encapsulated) could replace rifampicin and isoniazid during chemotherapy of murine tuberculosis. Alginate nanoparticles reduced the dosing frequency of azoles and ATDs by 15-fold. Alginate nanoparticles are the ideal carriers of azole and antitubercular drugs, which can reduce dosing frequency of azoles as well as ATDs for the better management of tuberculosis.
authors.affiliation: Center for Tuberculosis Research, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Zahoor
authors.initials: Z
authors.lastname: Ahmad
authors.forename: Sadhna
authors.initials: S
authors.lastname: Sharma
authors.forename: Gopal K
authors.initials: GK
authors.lastname: Khuller
mesh_terms: D000464:Alginates / Q000737:chemistry*; D000818:Animals; D000904:Antibiotics, Antitubercular / Q000008:administration & dosage* / Q000737:chemistry; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000737:chemistry; D001393:Azoles / Q000008:administration & dosage* / Q000737:chemistry; D002214:Capsules; D004058:Diffusion; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding / Q000379:methods; D004353:Drug Evaluation, Preclinical; D005260:Female; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D008297:Male; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D016896:Treatment Outcome; D014376:Tuberculosis / Q000188:drug therapy* / Q000473:pathology
chemical_list: D000464:Alginates; D000904:Antibiotics, Antitubercular; D000935:Antifungal Agents; D001393:Azoles; D002214:Capsules; D004337:Drug Carriers; D006603:Hexuronic Acids; D020723:Glucuronic Acid