Background: Tuberculosis (TB) is one of the major health challenge in the world. The current
treatment of TB needs daily administration of combined drug therapy for six or more months.
Sometime non-adherence and less bioavailability from current therapy develops multidrug resistance,
as a result, high dose requirement and subsequent intolerable toxicity are seen. Therefore, nanotechnology
gained special attention as it has potential to improve patient compliance, bioavailability
and reduction in dosing frequency.
Objective: The aim of this study is to fabricate alginate-chitosan nanoparticles (AL-CS NPs) under
appropriate conditions using ionic gelation method. The use of natural polymers in nanoparticle fabrication
has a vast application due to their biodegradability, biocompatibility and nontoxic nature.
Ionic gelation method involves the interaction between macromolecules with opposite charged ionizable
groups forming polyelectrolyte complex. Hence, it is rational to formulate natural polymerbased
sustained release nano-particulate matrix to improve patient adherence, reducing dose frequency
and drug toxicity.
Method: The formulations were based on 32 factorial designs. Nanoparticles of combined drug (Isoniazid-
INH and Pyrazinamide-PYZ) were fabricated using natural polymer. Formulation process involved
the use of pregelated sodium alginate followed by ionic gelation with chitosan. Pregelation of
sodium alginate included calcium chloride. The effects of sodium alginate concentration and chitosan
concentration on particle size, zeta potential, entrapment efficiency and in vitro drug release were studied.
Results: Optimized Batch-3s showed particle size 539.7 ± 2.33 nm, zeta potential -26.4 ± 0.55 mV,
and entrapment efficiency is 70.21 ± 0.24% and 73.45 ± 0.21% of INH and PYZ, respectively. Dissolution
release study of Batch-3s in 7.4 pH phosphate buffer exhibited the initial burst of 5.04 ±0.45%
and 19.68 ± 0.87% at 0.25 hrs followed by slow, sustained release of drug 74.53 ± 2.53 and 57.87 ±
2.04% at 10 hrs of INH and PYZ, respectively.
Conclusion: It concluded that chitosan (CS) and sodium alginate (AL) concentration are rate-limiting
factors in formulation development. Natural polymer based combined drug nano-particulate system
could be an innovative and optimistic approach in the treatment of TB.