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-lactide-co-glycolide (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.


CONCLUSIONS
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.
Pandey
Rajesh
R
Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Khuller
Gopal K
GK
D000284:Administration, Oral; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D005260:Female; D019344:Lactic Acid; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D049329:Nanostructures; D010949:Plasma / Q000737:chemistry; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers; D013307:Streptomycin / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D014376:Tuberculosis / Q000188:drug therapy* / Q000382:microbiology
D000900:Anti-Bacterial Agents; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D013307:Streptomycin