Abstract
Pharmacokinetic and chemotherapeutic studies have been carried out with aerosolised alginate nanoparticles encapsulating isoniazid (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 microm and geometric standard deviation of 1.71 +/- 0.1 microm. 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.
MeSH terms
-
Aerosols
-
Alginates / administration & dosage
-
Alginates / therapeutic use*
-
Animals
-
Antitubercular Agents / administration & dosage
-
Antitubercular Agents / pharmacokinetics
-
Antitubercular Agents / therapeutic use*
-
Drug Carriers / administration & dosage
-
Drug Carriers / therapeutic use*
-
Drug Evaluation, Preclinical
-
Female
-
Glucuronic Acid / administration & dosage
-
Glucuronic Acid / therapeutic use
-
Guinea Pigs
-
Hexuronic Acids / administration & dosage
-
Hexuronic Acids / therapeutic use
-
Inhalation
-
Isoniazid / administration & dosage
-
Isoniazid / pharmacokinetics
-
Isoniazid / therapeutic use*
-
Liver / metabolism
-
Lung / metabolism
-
Lung / microbiology
-
Male
-
Mycobacterium tuberculosis* / isolation & purification
-
Nanostructures / chemistry
-
Pyrazinamide / administration & dosage
-
Pyrazinamide / pharmacokinetics
-
Pyrazinamide / therapeutic use
-
Rifampin / administration & dosage
-
Rifampin / pharmacokinetics
-
Rifampin / therapeutic use
-
Spleen / metabolism
-
Spleen / microbiology
-
Time Factors
-
Tuberculosis / drug therapy*
-
Tuberculosis / metabolism
Substances
-
Aerosols
-
Alginates
-
Antitubercular Agents
-
Drug Carriers
-
Hexuronic Acids
-
Pyrazinamide
-
Glucuronic Acid
-
Isoniazid
-
Rifampin