PREPARATION AND CHARACTERIZATION OF ANDROGRAPHOLIDE NANOPARTICLES FOR VISCERAL LEISHMANIASIS CHEMOTHERAPY: IN VITRO AND IN VIVO EVALUATIONS
DOI:
https://doi.org/10.22159/ijpps.2016v8i12.14773Keywords:
Andrographolide, PLGA nanoparticles, In vitro activity, In vivo antileishmanial activity, Macrophage, Therapeutic indexAbstract
Objective: To overcome low physiological solubility, poor bioavailability, the short plasma half-life of andrographolide (AG), a delivery system based on poly (D, L-lactide-co-glycolide) (PLGA) nanoparticles (NPs) were developed to increase the efficiency of AG against visceral leishmaniasis (VL).
Methods: Andrographolide-PLGA nanoparticles (AGnp) were prepared with Pgp efflux inhibitor vitamin E TPGS (D-α-tocopheryl polyethylene glycol 1000 succinate) by emulsion solvent evaporation method and characterized. Antileishmanial activity was evaluated using in vitro and in vivo VL infection model.
Results: The particle size of AGnp was found to be171.4±11.5 nm with an encapsulation efficiency of 81%. The AGnp reduced AG cellular toxicity, retained it's in vitro antileishmanial activity and lead to a reduction (99.9%) of parasite burden in the Leishmania donovani infected spleen and liver. AGnp was more active in infected mice liver at low dose than in spleen. Therapeutic indexes (TI) were 6.9-fold greater in AG and 68-fold in AGnp compared to amphotericin B (AmB) when evaluated in L. donovani infected spleen.
Conclusion: Incorporation of AG in PLGA nanoparticles, provided controlled and improved in vivo performance against VL
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