Bio-evaluation of Poly-Lactate co-Glycolic Acid (PLGA) nanoparticles
loaded with radio-labeled rifampicin.
Abstract
The poly lactate co-glycolic acid (PLGA) nanoparticles of tubercular
drugs have been demonstrated to have sustained release profile over
seven days. There is no information on the location or mode of release
of these nanoparticles in living system. Therefore, we have planned the
study to explore the pharmacokinetics and biodistribution of PLGA
rifampicin nanoparticles in healthy human volunteers. Rifampicin was
labeled with 99mTc by indirect method and nanoparticles were prepared by
a single emulsion evaporation method. To investigate the
pharmacokinetics and biodistribution of nanoparticles, a single dose of
450 mg of rifampicin was administered orally to healthy human volunteers
divided into two different groups. Following a single oral dosage of the
rifampicin nanoformulation, the PK parameters were significantly
different between the nanoparticle and conventional groups AUC (113.8 vs
58.6), MRT (16.2 vs 5.8) and Ke (0.04 vs 0.10). Also SPECT/CT images
revealed bio-distrubution of nanoparticles in the distal portions of the
intestine, which is consistent with our dosimetry analysis Significant
difference in PK parameters and bio-distribution of nanoparticles in
spleen and lymph nodes with maximum deposition were observed in large
intestine. Nanoparticle distribution pattern may be advantageous for the
treatment of intestinal or lymph node TB and has the potential to result
in a lower dose of rifampicin nanoformulation for the treatment of
pulmonary TB.