Development, Characterization, and In Vitro Biological Performance of Amphotericin B and Terbinafine Microemulsions Against Leishmania major.

This study evaluated the effect of microemulsion (ME) containing Amphotericin B (AmB) alone and associated with Terbinafine (Tbf) on Leishmania major (L. major) using in vitro models. The ME formulations of these drugs were formulated and described. After evaluating their cytotoxicity on the J774A1 macrophage (MΦ), their potency against promastigotes and intracellular amastigotes models was evaluated using an in vitro MTT assay and Giemsa stain, respectively. Based on pseudo ternary phase diagrams, unloaded ME, Tbf-loaded ME (ME-Tbf), and, AmB-loaded ME (ME-AmB) with mean droplet sizes 3.4 ± 0.81, 10.05 ± 0.21, and 8.21 ± 0.46 were successfully prepared, respectively. Concerning toxicity, ME-AmB and ME-Tbf indicated lower toxicity on MΦs compared to the free drugs. The ME formulations showed considerably inhibitory effects compared to the free drug forms when the IC50 was examined. The IC50 values of AmB (59.19 ± 1.74 and 36.4 ± 3.2 µg/mL), ME-AmB (7.5 ± 0.9 and 0.8 ± 0.05 µg/mL), Tbf (234.5 ± 9 and 128.8 ± 0.28 µg/mL), ME-Tbf (26.27 ± 0.2 and 11.97 ± 0.6 µg/mL), AmB + Tbf (30.18 and 24.93 µg/mL), and ME-AmB + ME-Tbf (4.79 and 0.37 µg/mL) were estimated after 48 and 72 h, respectively.

Evaluation of the Efficacy of Amphotericin B and Terbinafine Microemulsions and Their Combination on Cutaneous Leishmaniasis and Comparison with the Conventional Drug Form in BALB/c Mice.

Intracellular parasitic protozoa of Leishmania sp. causes leishmaniasis. The restricted access of the drugs to affected cells in the treatment of intracellular infections such as leishmaniasis is frequently hampered. Furthermore, most of today's drugs have limited uses due to some containing toxic compounds, and drug resistance is on the rise. In the present investigation, Amphotericin B (AmB) and Terbinafine (Tbf) were loaded in microemulsion (ME) in combination and alone, and the in vivo efficacy was considered in BALB/c mice infected with Leishmania major (L. major). The wound size at the base of the mouse tail was measured, and real-time PCR was performed to quantify the parasite load after the infection challenge. The study demonstrated that the ME-AmB and ME-Tbf formulations are safe and effective compounds for the treatment of cutaneous leishmaniasis by enhancing the effectiveness of AmB and Tbf in reducing the parasite burden.