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Malaria is a vector-borne disease caused by mosquitoes infected with protozoan parasites belonging to Plasmodium species. In humans, five different Plasmodium species can cause infection—Plasmodium falciparum, Plasmodium vivax, Plasmodium malariae, Plasmodium knowlesi, and Plasmodium ovale. Significant progress in malaria disease control has been made in the last two decades, with a 62% reduction in the mortality rate between 2000 and 2019. Despite this success, malaria still accounted for approximately 228 million cases, and 405,000 deaths in 2018. The emergence of resistance in Plasmodium against currently available drugs, in addition to widespread resistance in mosquitoes, highlights the need for the development of better therapeutic modalities with novel mechanism(s) of action to kill the parasite. New therapies could be developed by finding new drug regimens, the development of new derivatives of current antimalarial drugs, or repurposing of approved drugs used for other diseases. There is also an emerging interest in the development of host-directed therapies against severe forms of malaria, particularly anti-inflammatory compounds and natural products that act on host immunity, and biological therapeutics that can control parasite growth, with or without antimalarial drugs. Host-targeted interventions could also help to improve the efficacy of the only approved malaria vaccine “Mosquirix” and the design of more effective vaccines in the future based on protein, DNA, and mRNA. The next generation of therapeutic modalities not only must eradicate the drug-resistant parasite but also must possess broad-spectrum to target multiple strains. In this chapter, we discuss the recent advances in antimalarial therapies and the emerging area of biological therapeutic modalities.

Plasmodium falciparum is resistant to all antimalarial drugs and a challenge for treatment. With this respect, formulations of antimalarial drugs with polymeric capsules with nanostructure carry a significant signature to suppress the resistance and to kill the Plasmodium falciparum. In this work, idiosyncratic hollow mesoporous polycaprolactone (ihmPCL) capsules were designed through ultrasonic-template synthesis approach with hollow core of dia. ca. ~ 450 nm and shell thickness of ca. ~ 30 nm and pore size of ca. ~ 8–9 nm. Then two formulations of ihmPCL capsules with Dihydroartemisinin (DHA) and Chloroquine diphosphate (CQDP) have been developed. ihmPCL capsules are capable to load 200.0 μg of DHA and 18.6 μg of CQDP per mg of capsules. With this formulation we can empowered to tune the doses of DHA and CQDP with time and temperature (30 °C–43 °C). It is observed that up to 143.20 μg (~71.6%) of DHA and 17.71 μg (~95.2%) of CQDP release can be controlled at different essential conditions which further can be sustained for longer period of time. Further, the half-maximum inhibitory concentration (IC50) have been investigated with these formulations and calculated to be 66.60 nM and 25.14 nM for DHA and CQDP, respectively in P. falciparum inhibition in vitro. Based on the unique release behaviour of these antimalarial drugs a 'temperature clock' module have been proposed for further accelerate the inhibition rate of P. falciparum infection. In conclusion, the PCL-DHA and PCL-CQDP formulations developed in this work could be effective in knocking down the P. falciparum infection and is paramount for treatment of malaria.