Alginate nanoparticles as antituberculosis drug carriers: formulation development, pharmacokinetics and therapeutic potential.
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.
Ahmad
Zahoor
Z
Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Pandey
Rajesh
R
Sharma
Sadhna
S
Khuller
G K
GK
D000464:Alginates / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000818:Animals; D000995:Antitubercular Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001672:Biocompatible Materials / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016503:Drug Delivery Systems; D004977:Ethambutol / Q000008:administration & dosage / Q000493:pharmacokinetics; D005260:Female; D020723:Glucuronic Acid / Q000493:pharmacokinetics / Q000627:therapeutic use; D006603:Hexuronic Acids / Q000493:pharmacokinetics / Q000627:therapeutic use; D007538:Isoniazid / Q000008:administration & dosage / Q000493:pharmacokinetics; D008297:Male; D051379:Mice; D053758:Nanoparticles / Q000627:therapeutic use*; D011718:Pyrazinamide / Q000008:administration & dosage / Q000493:pharmacokinetics; D012293:Rifampin / Q000008:administration & dosage / Q000493:pharmacokinetics; D014376:Tuberculosis / Q000188:drug therapy
D000464:Alginates; D000995:Antitubercular Agents; D001672:Biocompatible Materials; D006603:Hexuronic Acids; D011718:Pyrazinamide; D020723:Glucuronic Acid; D004977:Ethambutol; D007538:Isoniazid; D012293:Rifampin