期刊
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
卷 26, 期 4, 页码 298-303出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ijantimicag.2005.07.012
关键词
alginate; antitubercular drugs; tuberculosis; nebulisation
Pharmacokinetic and chemotherapeutic studies have been carried out with aerosolised alginate nanoparticles encapsulating isomazid (INH), rifampicin (RIF) and pyrazinamide (PZA). The nanoparticles were prepared by cation-induced gelification of alginate and were 235.5 +/- 0 nm in size, with drug encapsulation efficiencies of 70-90% for INH and PZA and 80-90% for RIF. The majority of particles (80.5%) were in the respirable range, with mass median aerodynamic diameter of 1.1 +/- 0.4 mu m and geometric standard deviation of 1.71 +/- 0.1 mu m. The relative bioavailabilities of all drugs encapsulated in alginate nanoparticles were significantly higher compared with oral free drugs. All drugs were detected in organs (lungs, liver and spleen) above the minimum inhibitory concentration until 15 days post nebulisation, whilst free drugs stayed up to day 1. The chemotherapeutic efficacy of three doses of drug-loaded alginate nanoparticles nebulised 15 days apart was comparable with 45 daily doses of oral free drugs. Thus, inhalable alginate nanoparticles can serve as an ideal carrier for the controlled release of antitubercular drugs. (c) 2005 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.
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