The aim of this study was to develop novel nanoemuslion core loaded nanocapsules (NCs) with high payload of doxorubicin (DOX) and to assess its efficacy against Leishmania donovani. The low energy emulsification method was used to obtained nanoemulsion core as template, followed by stepwise addition of additional layer components protamine sulphate and sodium alginate. Zeta potential studies revealed that there was reversal in charge after each layering. NCs were characterized on the basis of size (340 nm) and entrapment efficiency (>80%). The drug release behaviour was studied by in vitro method. The NCs loaded with DOX (NCs-DOX) is completely internalized into macrophages showing improved efficacy (IC50 of formulation is almost <= 1.9-fold as compared to plain drug, p < 0.05) against intracellular amastigotes.