Development of 4-sulfated N-acetyl galactosamine anchored chitosan nanoparticles: a dual strategy for effective management of Leishmaniasis

Abstract

The present investigation reports the modification of chitosan nanoparticles with a ligand 4-sulfated N-acetyl galactosamine (4-SO₄GalNAc) for efficient chemotherapy in leishmaniasis (SCNPs) by using dual strategy of targeting. These (SCNPs) were loaded with amphotericin B (AmB) for specific delivery to infected macrophages. Developed AmB loaded SCNPs (AmB-SCNPs) had mean particle size of 333 ± 7 nm, and showed negative zeta potential (−13.9 ± 0.016 mV). Flow cytometric analysis revealed enhanced uptake of AmB–SCNPs in J774A.1, when compared to AmB loaded unmodified chitosan NPs (AmB–CNPs). AmB–SCNPs provide significantly higher localization of AmB in liver and spleen as compared to AmB–CNPs after i.v. administration. The study stipulates that 4-SO₄GalNAc assures of targeting, resident macrophages. Highly significant anti-leishmanial activity (P < 0.05 compared with AmB–CNPs) was observed with AmB–SCNPs, causing 75.30 ± 3.76% inhibition of splenic parasitic burdens. AmB–CNPs and plain AmB caused only 63.89 ± 3.44% and 47.56 ± 2.37% parasite inhibition, respectively, in Leishmania-infected hamsters (P < 0.01 for AmB–SCNPs versus plain AmB and AmB–CNPs versus plain AmB).