In vitro evaluation of activatable melittin encapsulated in liposome and albumin nanoparticles against Leishmania

Document Type : Original Article

Authors

1 Department of Animal Science, Faculty of Agriculture, University of Kurdistan, Sanandaj, Iran

2 Department of Parasitology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran

3 Rastegar Reference Laboratory, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran

Abstract
Leishmaniasis comprises a spectrum of clinical manifestations caused by protozoan parasites of the genus Leishmania, order Trypanosomatida. Cutaneous leishmaniasis remains a significant zoonotic disease prevalent in tropical and subtropical regions, particularly in developing countries. Despite ongoing research, a definitive cure for this parasitic infection is still needed. This study explored the potential of activatable melittin (AM) as a selective treatment for cutaneous leishmaniasis caused by Leishmania major. The AM was designed using PepFold and ExPASy servers, incorporating a matrix metalloproteinase -2/9 cleavable linker to target L. major-infected macrophages selectively. To enhance drug delivery and reduce potential toxicity, AM was encapsulated within albumin nanoparticles and liposomes. The anti-leishmanial efficacy of these formulations was evaluated at AM concentrations ranging from 25.00 to 100 µg mL-1 over 48 hr, with each experiment performed in 10 independent replicates (n = 10 per group). Statistical analysis using one-way ANOVA followed by Tukey's post-hoc test revealed a significant reduction in the average number of intracellular amastigotes per macrophage in the liposome-treated and albumin nanoparticle-treated groups (7.00 ± 1.50 amastigotes per macrophage) compared to the untreated infected control group (35.00 ± 3.20 amastigotes per macrophage). Treatment with 25.00 µg mL-1 of AM encapsulated in non-toxic albumin nanoparticles and liposomes demonstrated the most promising anti-leishmanial effect, resulting in an approximately 80.00% reduction in intracellular L. major amastigotes (compared to control).

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Volume 17, Issue 2
February 2026
Pages 127-133

  • Receive Date 28 December 2024
  • Revise Date 12 May 2025
  • Accept Date 14 July 2025