A novel oral combination strategy for malaria treatment based on artemisinin and apigenin co-loaded in silica-doped nutriosomes

Malaria is a major global health problem that causes substantial socioeconomic losses in developing countries and is associated with high morbidity and mortality, particularly in endemic areas. For these reasons, access to effective pharmacological therapies and adequate healthcare services is essential for the prevention, treatment, and control of malaria. In the present study, an advanced oral drug delivery system based on mesoporous silica-doped nutriosomes co-loaded with apigenin and artemisinin was developed to improve malaria therapy. Vesicles were prepared with phosphatidylcholine and increasing amounts of Nutriose® FM06 . To stably load apigenin, a carbonate-bicarbonate buffer solution at pH 9 was used as hydrating medium. Unfortunately, this pH condition promoted the degradation of artemisinin, leading to the formation of non-peroxidic analogues, which are known to be less effective in malaria treatment. Nevertheless, the resulting nutriosomes exhibited in vitro antiplasmodial activity, with IC 50 and IC 90 values against Plasmodium falciparum comparable to those of artemisinin solution. Moreover, when orally administered at the IC 90 dose to infected mice, the formulation resulted in survival rates similar to those observed for artemisinin solution. These findings provide an encouraging proof of concept for the proposed formulation. They demonstrate the potential of this delivery strategy to improve oral antimalarial therapy and establish a solid basis for further pharmacological and in vivo investigations aimed at optimizing and fully evaluating the system.