Chemotherapeutic evaluation of alginate nanoparticle-encapsulated azole antifungal and antitubercular drugs against murine tuberculosis

摘要

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.