title: 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).
authors.affiliation: Pharmaceutics Division, CSIR-Central Drug Research Institute, Lucknow 226031, India.
authors.forename: Priyanka
authors.initials: P
authors.lastname: Tripathi
authors.affiliation: Pharmaceutics Division, CSIR-Central Drug Research Institute, Lucknow 226031, India.
authors.forename: Pankaj
authors.initials: P
authors.lastname: Dwivedi
authors.affiliation: Pharmaceutics Division, CSIR-Central Drug Research Institute, Lucknow 226031, India.
authors.forename: Renuka
authors.initials: R
authors.lastname: Khatik
authors.affiliation: Parasitology Division, CSIR-Central Drug Research Institute, Lucknow 226031, India.
authors.forename: Anil Kumar
authors.initials: AK
authors.lastname: Jaiswal
authors.affiliation: Parasitology Division, CSIR-Central Drug Research Institute, Lucknow 226031, India.
authors.forename: Anuradha
authors.initials: A
authors.lastname: Dube
authors.affiliation: Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute, Lucknow 226031, India.
authors.forename: Poonam
authors.initials: P
authors.lastname: Shukla
authors.affiliation: Pharmaceutics Division, CSIR-Central Drug Research Institute, Lucknow 226031, India. Electronic address: mishrapr@hotmail.com.
authors.forename: Prabhat Ranjan
authors.initials: PR
authors.lastname: Mishra
mesh_terms: D000116:Acetylgalactosamine / Q000737:chemistry*; D000666:Amphotericin B / Q000008:administration & dosage*; D000818:Animals; D002460:Cell Line; D048271:Chitosan / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D007896:Leishmaniasis / Q000188:drug therapy*; D008264:Macrophages / Q000469:parasitology; D051379:Mice; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles; D017550:Spectroscopy, Fourier Transform Infrared; D013431:Sulfates / Q000737:chemistry*
chemical_list: D013431:Sulfates; D000666:Amphotericin B; D048271:Chitosan; D000116:Acetylgalactosamine
keywords: 4-Sulfated N-acetyl galactosamine; Chitosan nanoparticles; Dual strategy; Macrophages; Mannose receptors