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  • Title: Pharmacokinetic and pharmacodynamic behaviour of antitubercular drugs encapsulated in alginate nanoparticles at two doses.
    Author: Ahmad Z, Pandey R, Sharma S, Khuller GK.
    Journal: Int J Antimicrob Agents; 2006 May; 27(5):409-16. PubMed ID: 16624533.
    Abstract:
    This study was designed to evaluate the pharmacokinetics and tissue distribution of free and alginate-encapsulated antitubercular drugs in mice at different doses. Alginate nanoparticles encapsulating isoniazid (INH), rifampicin (RIF), pyrazinamide (PZA) and ethambutol (EMB) were prepared by controlled cation-induced gelification of alginate. The formulation was orally administered to mice at two dose levels (D1 and D2). A comparison was made in mice receiving free drugs at equivalent doses. Drugs were analysed by high performance liquid chromatography (HPLC). The average size of alginate nanoparticles was found to be 235.5+/-0.0 nm with a polydispersity index of 0.44; drug encapsulation was 70-90% for INH and PZA, 80-90% for RIF and 88-95% for EMB. In the free drug groups, plasma levels of RIF and INH were higher and PZA and EMB levels were lower in the D1 group (per body surface area of mice) compared with the D2 group (recommended human dose). The plasma drug levels of all drugs were higher in the D1 encapsulated group compared with D2, resulting in higher values of area under the plasma drug concentration-time curve (AUC(0-infinity)). The relative bioavailabilities of all drugs encapsulated in alginate nanoparticles were significantly higher compared with free drugs. Drug levels were maintained at or above the minimum inhibitory concentration (MIC(90)) until Day 15 in organs after administration of encapsulated drugs, whilst free drugs stayed at or above the MIC(90) up to Day 1 only irrespective of dose. The levels of drugs in various organs remained above the MIC at both doses for equal periods, demonstrating their equiefficiency. Alginate nanoparticles hold great potential in reducing dosing frequency of antitubercular drugs.
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