Tuberculosis (TB) caused by Mycobacterium
tuberculosis has afflicted the human race for
centuries. Even though a vaccine and
numerous effective antimycobacterial agents
are available for its treatment, even in the 21st
century, several million people still die from this
disease each year1
. The main problems
associated with the anti-TB drug therapy
include loss of efficacy through bacterial
resistance, side effects, and low patient
compliance2,3. In the development of ideal TB
therapy, two points are considered to be
important. First, the metabolism of M.
tuberculosis is slow, resulting in a generation
time that is measured in hours. This means
that drug regimens should ideally have a low
level of toxicity for long-term administration,
and if possible, should be bactericidal so that
elimination of the organism is rapid and is not
totally dependent on the immune system.
Second, the tubercle bacillus is a facultative
intracellular parasite4,5. Therefore, drugs
should also be able to penetrate host cells.
Thus, an ideal method for treating tuberculosis
would be one that not only is able to safely
deliver drugs systemically for prolonged
duration, but also would be able to target drugs
to the intracellular environment in which the
tubercle bacilli are found6
. Isoniazid (INH) is a
key component of the fixed dose combination
(FDC) therapy used for first line therapy of TB
as it can penetrate the host cells. However, the
drug is characterized by a short half-life