Alginate nanoparticles as antituberculosis drug carriers: formulation development, pharmacokinetics and therapeutic potential.
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2006-07-10
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Abstract
BACKGROUND: Reduction in the dosing frequency of antituberculosis drugs (ATDs) by applying drug delivery technology has the potential to improve the patient compliance in tuberculosis (TB). Alginate (a natural polymer) based nanoparticulate delivery system was developed for frontline ATDs (rifampicin, isoniazid, pyrazinamide and ethambutol).
METHODS: Alginate nanoparticles were prepared by the controlled cation induced gelification method and administered orally to mice. The drug levels were analysed by high performance liquid chromatography (HPLC) in plasma/tissues. The therapeutic efficacy was evaluated in M. tuberculosis H37Rv infected mice.
RESULTS: High drug encapsulation efficiency was achieved in alginate nanoparticles, ranging from 70%-90%. A single oral dose resulted in therapeutic drug concentrations in the plasma for 7-11 days and in the organs (lungs, liver and spleen) for 15 days. In comparison to free drugs (which were cleared from plasma/organs within 12-24 h), there was a significant enhancement in the relative bioavailability of encapsulated drugs. In TB-infected mice three oral doses of the formulation spaced 15 days apart resulted in complete bacterial clearance from the organs, compared to 45 conventional doses of orally administered free drugs.
CONCLUSIONS: Alginate nanoparticles appear to have the potential for intermittent therapy of TB.
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Ahmad Z, Pandey R, Sharma S, Khuller GK. Alginate nanoparticles as antituberculosis drug carriers: formulation development, pharmacokinetics and therapeutic potential. The Indian Journal of Chest Diseases & Allied Sciences. 2006 Jul-Sep; 48(3): 171-6