INTRODUCTION
“ Tuberculosis (TB), often regarded as a disease of the past, is still one of the leading” causes of mortality among adults and children. Each year, globally, around 10.4 million individuals develop TB infection, while1.8 million people die due to this disease 1.
Among the arsenal of anti-tubercular drugs, rifampicin is one of the most effective agents 2 3. It is the only mycobactericidal drug that kills both dividing as well as non-dividing bacteria, and can eliminate up to 99% of tubercle bacilli within two months of commencement of TB treatment 4. Rifampicin is also used against meningococcal meningitis, “methicillin-resistant Staphylococcus aureus  (MRSA),Neisseria gonorrhoeaeHaemophilus influenzae , and Legionella pneumophila infections”5. Unfortunately, mycobacterium responds slowly to rifampicin, resulting in prolonged infectiousness or acquired drug resistance, as well as increasing the cost on public health systems by extending treatment duration (9). Low plasma drug levels due to insufficient dose and non-adherence also explain the sluggish response 5.
Sustained therapeutic drug levels can be achieved using controlled-release nanoformulation of rifampicin 6. A number of biodegradable polymers have been tried for the purpose of drug encapsulation 7. Of these, poly lactic-co-glycolic acid (PLGA) is the most widely used because of its favorable safety profile, bio-compatibility and degradation characteristics8. “It is possible to change the overall physical properties of the polymer-drug matrix by controlling the relevant parameters, such as polymer molecular weight, ratio of lactide to glycolide, and drug concentration, to achieve a desired release profile8. However, the potential toxicity associated with dose dumping, inconsistent release, and distribution of PLGA nanoformulation is still unclear and requires further evaluation4. Radiolabeled pharmaceuticals and mass balance excretion studies are being increasingly conducted to track the bio-disposition of drugs as well the pharmaceutical excipients inside the body 9 10.
PK studies carried out on rifampicin and other anti-tubercular drugs by our group have revealed that nano-encapsulation in PLGA provides a sustained release for up to one week after single-dose oral administration in animals 11. However, the exact pathway of biodisposition of PLGA nanoparticles loaded with rifampicin in human remains unknown. Non-invasive in-vivo imaging (SPECT/CT) techniques are integral part of biodistribution and PK/PD studies12. Therefore, we planned to evaluate the PK profile and detailed biodisposition of radio-labeled rifampicin entrapped in PLGA nanoparticles.