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Indian Journal of Experimental Biology (IJEB) >
IJEB Vol.44 [2006] >
IJEB Vol.44(06) [June 2006] >
| Title: | Oral poly(lactide-co-glycolide) nanoparticle based antituberculosis drug delivery: Toxicological and chemotherapeutic implications |
| Authors: | Pandey, Rajesh
Sharma, Sadhna
Khuller, G K |
| Keywords: | Chemotherapy
Nanoparticles
Poly(lactide-co-glycolide)
Toxicity
Tuberculosis |
| Issue Date: | Jun-2006 |
| Publisher: | CSIR |
| Abstract: | The present study reports on the detailed toxicological and
chemotherapeutic evaluation of antituberculosis drug loaded nanoparticles in
mice. A single oral dose administration of poly(lactide-co-glycolide) (PLG, a
synthetic polymer) nanoparticles containing
rifampicin+isoniazid+pyrazinamide+ethambutol could maintain drug levels in
various tissues for 9-10 days and did not elicit any adverse response even when
administered at several fold higher than the recommended therapeutic dose.
However, dosing with conventional free drugs at the equivalent higher doses was
lethal. Despite multiple oral dosing with the formulation at every 10th
day, no toxicity was observed on the completion of subacute (28 days) or
chronic (90 days) toxicity studies based on survival, gross pathology,
histopathology, blood biochemistry and hematology. In mice harboring a high
mycobacterial load (mimicking human tuberculosis), two independent
chemotherapeutic regimens, i.e. 5 doses of PLG nanoparticles encapsulating
(rifampicin+isoniazid+pyrazinamide+ethambutol) administered 10 days apart, or 2
doses of the 4-drug formulation followed by 3 doses of 2-drug formulation
(rifampicin+isoniazid) resulted in undetectable bacilli. Further, the efficacy
was comparable to 46 daily doses of oral free drugs. Therefore, the
experimental evidence suggests that PLG nanoparticle-based
antituberculosis drug delivery system is safe and well suited for prolonged
and intermittent oral chemotherapy. |
| Page(s): | 459-467 |
| ISSN: | 0975-1009 (Online); 0019-5189 (Print) |
| Source: | IJEB Vol.44(06) [June 2006]
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