title: Chitosan-assisted immunotherapy for intervention of experimental leishmaniasis via amphotericin B-loaded solid lipid nanoparticles.
abstract: Solid lipid nanoparticles (SLNs) have emerged as an excellent substitute over polymeric nanoparticles and, when incorporated with chitosan which activates the macrophage to impart an immune response, produce excellent results to fight against deleterious diseases like leishmaniasis where its parasite diminishes the immunity of the host to induce resistance. Based upon this hypothesis, chitosan-coated SLNs were developed and loaded with amphotericin B (AmB) for immunoadjuvant chemotherapy of Leishmania infection. Both uncoated and chitosan-coated AmB-loaded SLNs (AmB-SLNs) were fabricated using solvent emulsification and evaporation method. The various processes and formulation parameters involved in AmB-SLN preparation were optimized with respect to particle size and stability of the particles. In vitro hemolytic test credited the formulations to be safe when injected in the veins. The cellular uptake analysis demonstrated that the chitosan-coated AmB-SLN was more efficiently internalized into the J774A.1 cells. The in vitro antileishmanial activity revealed their high potency against Leishmania-infected cells in which chitosan-coated AmB-SLNs were distinguishedly efficacious over commercial formulations (AmBisome and Fungizone). An in vitro cytokine estimation study revealed that chitosan-coated AmB-SLNs activated the macrophages to impart a specific immune response through enhanced production of TNF-α and IL-12 with respect to normal control. Furthermore, cytotoxic studies in macrophages and acute toxicity studies in mice evidenced the better safety profile of developed formulation in comparison to marketed formulations. This study indicates that the AmB-SLNs are a safe and efficacious drug delivery system which promises strong competence in antileishmanial chemotherapy and immunotherapy.
authors.affiliation: Pharmaceutics Division, CSIR-Central Drug Research Institute, Lucknow, 226031, UP, India.
authors.forename: Vineet
authors.initials: V
authors.lastname: Jain
authors.affiliation: Pharmaceutics Division, CSIR-Central Drug Research Institute, Lucknow, 226031, UP, India.
authors.forename: Annie
authors.initials: A
authors.lastname: Gupta
authors.affiliation: Pharmaceutics Division, CSIR-Central Drug Research Institute, Lucknow, 226031, UP, India.
authors.forename: Vivek K
authors.initials: VK
authors.lastname: Pawar
authors.affiliation: Pharmaceutics Division, CSIR-Central Drug Research Institute, Lucknow, 226031, UP, India.
authors.forename: Shalini
authors.initials: S
authors.lastname: Asthana
authors.affiliation: Parasitology Division, CSIR-Central Drug Research Institute, Lucknow, 226031, UP, India.
authors.forename: Anil K
authors.initials: AK
authors.lastname: Jaiswal
authors.affiliation: Parasitology Division, CSIR-Central Drug Research Institute, Lucknow, 226031, UP, India.
authors.forename: Anuradha
authors.initials: A
authors.lastname: Dube
authors.affiliation: Pharmaceutics Division, CSIR-Central Drug Research Institute, Lucknow, 226031, UP, India. manish_chourasia@cdri.res.in.
authors.forename: Manish K
authors.initials: MK
authors.lastname: Chourasia
mesh_terms: D000666:Amphotericin B / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000981:Antiprotozoal Agents / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D048271:Chitosan / Q000494:pharmacology*; D004655:Emulsions / Q000737:chemistry / Q000494:pharmacology; D007167:Immunotherapy; D007893:Leishmania donovani; D007898:Leishmaniasis, Visceral / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D008055:Lipids / Q000737:chemistry / Q000494:pharmacology; D051379:Mice; D053758:Nanoparticles
chemical_list: D000981:Antiprotozoal Agents; D004655:Emulsions; D008055:Lipids; D000666:Amphotericin B; D048271:Chitosan