fabrication and evaluation of the effect of niosomal doxycycline with artemisinin plant extract on leishmania major in vitro and in vivo

Aim and background: leishmania major(l. major) is an intracellular pathogen causing cutaneous leishmaniasis(cl). cl is a major public health problem in worldwide. unfortunately, current anti-leishmanial drugs have had limited clinical efficacy. therefore, this study is done to find the effects of niosomal doxycycline(ndx), niosomal artemisia sieberi essential oil(na), and niosomal doxycycline with artemisia sieberi essential oil(ndxa) on leishmania major in vitro and in vivo. methods: all 3 niosomal formulations were produced by thin film hydration method and the effects of their various concentration (0.125-1 mg/ml) on leishmania major promastigotes were assessed by flow cytometry. also, the toxicity of each formulation on j774 cell line was calculated. the efficacy of each niosomal formulation in treating cutaneous leishmaniasis lesions in balb/c inbred mice was evaluated. results and discussion: flowcytometry results showed that ndx, na and ndxa at concentration of 1mg/ml have the highest lethal effect on l. major promastigotes(69.17% ,65.12%, 87.11% respectively). the lowest level of lethality for all three compounds (33.42%, 38.72%, and 49.13%, respectively) was observed at a concentration of 0.125 mg/ml. ic50 for the mentioned compounds were 2.07mg/ml, 4.91mg/ml, 1.69mg/ml respectively. in vivo, all compounds reduced wound size after three weeks of treatment. ndxa revealed the best efficiency and showed a significant reduction in comparison with negative control group(p= 0.043). conclusion: in conclusion, this study demonstrates that niosomal doxycycline with artemisinin plant extract has dose-dependent effects on the mortality of l. major promastigotes and could be a promising treatment option for cutaneous leishmaniasis.