Coalition of Biological Agent (Melatonin) With Chemotherapeutic Agent (Amphotericin B) for Combating Visceral Leishmaniasis via Oral Administration of Modified Solid Lipid Nanoparticles.

Abstract

In this study, 2-hydroxypropyl-β-cyclodextrin (HPβCD) grafted solid lipid nanoparticle (SLN)-based bioconjugate was synthesized and used for administering a combination of melatonin (Mel) and amphotericin B (AmB) orally for effective visceral leishmaniasis (VL) treatment. The formulations (HPCD-Mel-AmB SLN) were synthesized by the emulsion solvent evaporation method. HPCD-Mel-AmB SLN showed a high loading capacity and a high entrapment efficiency of AmB (% DL = 9.0 ± 0.55 and % EE = 87.9 ± 0.57) and Mel (% DL = 7.5 ± 0.51 and % EE = 63 ± 6.24). The cumulative percent release of AmB and Mel was 66.10 and 73.06%, respectively, up to 72 h. Time-dependent cellular uptake was noticed for HPCD-Mel-AmB SLN for 4 h. Further, HPCD-Mel-AmB SLN did not show any toxic effects on J774A.1 macrophages and Swiss albino mice. HPCD-Mel-AmB SLN (10 mg/kg ×5 days, p.o.) has significantly diminished (98.89%) the intracellular parasite load in liver tissues of L. donovani-infected BALB/c mice, subsequently highlighting the role of melatonin toward an effective strategy in combating leishmanial infection. Therefore, these results indicated that administration of HPCD-Mel-AmB SLN improve the therapeutic index of the first-line drug in addition to the introduction of biological agent and would be a promising therapeutic candidate for effective VL therapy. In the present study, the objective is to test the efficacy of the chemotherapeutic approach in combination with a biological immunomodulatory agent against leishmanial infection using in vitro and in vivo studies. This information suggests that melatonin could be an efficacious and potent antileishmanial agent.