The combination of the active compounds curcumin and piperine (CP) is effective as an antimalarial; however, the solubility and bioavailability of CP are very low. This study aims to formulate CP in nanoparticles (NP), which are then fabricated into dissolving microneedles (DMN). The NPs were prepared with a concentration ratio of CP-Chitosan-So.TPP-So.Alginate (0.1:0.04:0.02:0.03). Subsequently, NPs-CP-DMN were formulated with NPs-CP concentrations (35:40:50 w/w) and a mixture of the polymers polyvinyl alcohol (PVA) and polyvinylpyrrolidone (PVP) in a ratio of (35:65, 40:60, 50:50). Characterization of the nanoparticles and microneedles was conducted, including dissolution time tests, permeation studies, hemolysis assessment, dermatokinetics, and in vitro antiplasmodial activity testing. The results showed that NPs-CP had an average size of 446.67 ± 40.27 nm and 367.6 ± 26.31 nm. On the formula NPs-CP-DMN the addition of PVA and PVP polymers (F2) resulted in DMNs with good mechanical strength and penetration ability, capable of penetrating five layers of Parafilm®. This formulation completely dissolved in 10 min without leaving any residue, with a curcumin flux value of 25.7 ± 0,51 µg/mL and piperine flux of 28.5 ± 0,51 µg/mL. The formulation showed no toxicity, with a hemolysis percentage of < 5 %, Tmax of 7 h, and Cmax values of 11.07 ± 0.31 µg/cm3 for curcumin and 17.40 ± 3.3 µg/cm3 for piperine. Moreover, this formulation effectively inhibited the P.falciparum FCR3 strain parasite, with an IC50 value of 35.9 μg/mL. Therefore, this study holds promise as a new strategy for malaria treatment.
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