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).

Keywords: 4-Sulfated N-acetyl galactosamine; Chitosan nanoparticles; Dual strategy; Macrophages; Mannose receptors.