Nanoparticle-based oral drug delivery system for an injectable antibiotic - Streptomycin - Evaluation in a murine tuberculosis model

Background: To develop an oral drug delivery system for an injectable antibiotic, streptomycin. Methods: Poly-lactidecoglycolide ( PLG) nanoparticles encapsulating streptomycin were prepared by the multiple emulsion technique and administered orally to mice for biodistribution and chemotherapeutic studies. Results: The mean particle size was 153.12 nm with 32.12 +/- 4.08% drug encapsulation and 14.28 +/- 2.83% drug loading. Streptomycin levels were maintained for 4 days in the plasma and for 7 days in the organs following a single oral administration of PLG nanoparticles. There was a 21-fold increase in the relative bioavailability of PLG-encapsulated streptomycin compared with intramuscular free drug. In Mycobacterium tuberculosis H-37 Rv infected mice, eight doses of the oral streptomycin formulation administered weekly were comparable to 24 intramuscular injections of free streptomycin. Further, the nanoparticle formulation did not result in nephrotoxicity as assessed on a biochemical basis. Conclusion: Our results suggest that nanoencapsulation might be useful for developing a suitable oral dosage form for streptomycin and perhaps for other antibiotics that are otherwise injectable.