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.

Preparation, characterization, and evaluation of amphotericin B-loaded MPEG-PCL-g-PEI micelles for local treatment of oral <em>Candida albicans</em>

“…Then, the culture medium was removed by pipette. Fungizone (a micellar dispersion of AmB with DOC), 38,39 AmB/MPP micelles, and MPP blank micelles were added to each well and incubated at 37°C for a certain time. Following incubation, 20 μL of 5 mg/ mL MTT in PBS was put into each well and then incubated for 4 h at 37°C.…”

A Review of Nanotechnology for Targeted Anti-schistosomal Therapy

“…Further to this, targeted nano-enabled drug delivery of a 19-amino peptide from the circumsporozoite protein of Plasmodium berghei which contained a conserved region, as a consensus heparin sulfate proteoglycan-binding sequence attached to the distal end of a lipid-polyethylene glycol bioconjugated, was prepared by the incorporation into phosphatidylcholine liposomes, reflecting favorable in vitro results (Longmuir et al, 2006). Jain et al (2014) developed a chitosan-assisted immunotherapy for the intervention of experimental leishmaniasis via amphotericin B -SLPs to activate the macrophages in order to impart a specific immune response by improving the production of TNF-α and IL-12 (Jain et al, 2014). This study also reflected a positive hypothesis for targeted nano-drug delivery for site specific targeting.…”

Nanotechnological Strategies for Treatment of Leishmaniasis—A Review

“…The therapeutic potential of SLNs has been evaluated in different studies such as cancer 126 and parasitic diseases such as malaria, 127 human African trypanosomiasis 128 and CL. 129 Particularly for CL, SLNs could improve the interaction of the drug with the stratum corneum and other layers of the skin and thus provide the possibility of topical administration with controlled release, reduced drug toxicity and so to optimize its treatment. 129 130 Paramomycincontaining SLN has been previously described 130 and showed potent activity against L. major and L. tropica intracellular amastigotes when compared to free paromomycin; the cytotoxicity of paramomycin-SLN formulation is size dependent.…”