Background: Tuberculosis (TB) is infectious, contagious and persistent infection caused by
Mycobacterium tuberculosis. The treatment of TB is becoming more complex due to development of
multidrug resistant tuberculosis hence, it requires daily administration of combined drug therapy for
six or more months. It is rational to formulate controlled release formulation to reduce dosing frequency
and drug toxicity. Chitosan Nanoparticles (CHNPs) are optimistic approach to treat tuberculosis.
Objective: To formulate combined drug chitosan nanoparticles of antitubercular drugs (Isoniazid-INH
and Pyrazinamide-PYZ) to get additive effect on Mycobacterium tuberculosis. Nanoparticles are colloidal
system that enhances effective permeation through cell membrane, stability in blood stream and
controlled release of drug. Hence, it is emerging as a new weapon in drug delivery field.
Methods: The 32 factorial design was used to formulate nanoparticles by ionic gelation method using
Chitosan (CS) and sodium tripolyphosphate (TPP) with ratio 3:1 (CS:TPP::v/v) in pH range 4.6 to 4.8.
The effect of CS and TPP concentration on particle size, zeta potential, entrapment efficiency and in
vitro drug release were studied.
Results: Optimized batch 8N showed particle size 414.3 ± 2.71 nm, zeta potential 26.52 ± 0.67mV,
PDI (poly dispersity index) 0.296 and entrapment efficiency of INH and PYZ 55.29 ± 0.06% and
63.14 ± 0.29% respectively. Dissolution release study of 8N formulation at pH 7.4 showed initial burst
release of 20.28 ± 1.43% and 23.62 ± 1.07 at 0.25 hrs followed by controlled release up to 84.82 ±
2.54% and 61.48 ± 1.52% by INH and PYZ for 14 hrs.
Conclusion: The study concluded that CS and TPP concentration were rate limiting factors in optimizing
formulation development. Combined drug nanoparticle system has an innovative and optimistic
approach towards the enhancement of therapeutic efficacy and reduction undesirable effects of antitubercular