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 gonorrhoeae , Haemophilus 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.