Enhanced paromomycin efficacy by solid lipid nanoparticle formulation against Leishmania in mice model

• Published in: Parasite immunology 2016-10, Vol.38 (10), p.599-608
• Main Authors: Heidari‐Kharaji, M., Taheri, T., Doroud, D., Habibzadeh, S., Badirzadeh, A., Rafati, S.
• Format: Article
• Language: English
• Subjects: Animals; Antiprotozoal Agents - administration & dosage; Antiprotozoal Agents - pharmacology; cutaneous leishmaniasis; cytokine; Cytokines - metabolism; Disease Models, Animal; Drug Carriers; Drug Compounding; drug delivery system; Female; Interferon-gamma - metabolism; Interleukin-4 - metabolism; Leishmania - drug effects; Leishmaniasis - drug therapy; Leishmaniasis - parasitology; Lipids; Mice; Mice, Inbred BALB C; Nanoparticles; Nitric Oxide - metabolism; Paromomycin - administration & dosage; Paromomycin - pharmacology; paromomycin sulphate; solid lipid nanoparticle; therapy
• ISSN: 0141-9838; 1365-3024
• DOI: 10.1111/pim.12340

Summary Leishmaniasis caused by protozoan parasites of the genus Leishmania. Intracellular infections treatment such as leishmaniasis is frequently hampered by limited access of drugs to infected cells. Moreover, most of the current drugs are confined to some toxic compounds, and there are increasing incidences of development of drug resistance. Hence, production of a new antileishmanial compound is crucial. Paromomycin sulphate (PM) is a promising antileishmanial drug. One strategy to improve drug effectiveness is to use appropriate delivery systems. Solid lipid nanoparticle (SLN) is as an excellent substitute delivery system to other colloidal carrier. In the present study, PM was loaded in solid lipid nanoparticles (PM‐SLN) and the in vivo efficacy was studied against Leishmania (L.) major‐infected BALB/c mice. For this reason, the footpad swelling was measured and real‐time PCR was performed to quantify the parasite load after infectious challenge. The level of cytokines including interleukin‐4 (IL‐4) and gamma interferon (IFN‐γ) and nitric oxide was evaluated. Altogether, this study showed that the PM‐SLN formulation is a safe compound and SLN in PM‐SLN compound is effective for treatment of leishmaniasis by improving the effectiveness of PM in killing the parasite and switching towards Th1 response.