Faculty of Veterinary Medicine, Urmia University Veterinary Research Forum 2008-8140 17 2 2026 02 01 In vitro evaluation of activatable melittin encapsulated in liposome and albumin nanoparticles against Leishmania 127 133 733520 10.30466/vrf.2025.2047654.4572 EN Soheila Akhzari Department of Animal Science, Faculty of Agriculture, University of Kurdistan, Sanandaj, Iran Sedigheh Nabian Department of Parasitology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran 0000-0002-2350-4151 Mohammad Taheri Rastegar Reference Laboratory, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran Journal Article 2024 12 28 Leishmaniasis comprises a spectrum of clinical manifestations caused by protozoan parasites of the genus <em>Leishmania</em>, 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 <em>Leishmania major</em>. The AM was designed using PepFold and ExPASy servers, incorporating a matrix metalloproteinase -2/9 cleavable linker to target <em>L. major</em>-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 <em>per</em> group). Statistical analysis using one-way ANOVA followed by Tukey's <em>post-hoc t</em>est revealed a significant reduction in the average number of intracellular amastigotes <em>per </em>macrophage in the liposome-treated and albumin nanoparticle-treated groups (7.00 ± 1.50 amastigotes <em>per </em>macrophage) compared to the untreated infected control group (35.00 ± 3.20 amastigotes <em>per </em>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 <em>L. major</em> amastigotes (compared to control). https://vrf.iranjournals.ir/article_733520_efafc6d05562d132243971794c17ecb6.pdf