Nanomedicines for Malaria Chemotherapy: Encapsulation vs. Polymer Therapeutics

Abstract

Malaria is one of the oldest infectious diseases that afflict humans and its history extends back for millennia. It was once prevalent throughout the globe but today it is mainly endemic to tropical regions like sub-Saharan Africa and Southeast Asia. Ironically, treatment for malaria has existed for centuries yet it still exerts an enormous death toll. This contradiction is attributed in part to the rapid development of resistance by the malaria parasite to chemotherapeutic drugs. In turn, resistance has been fuelled by poor patient compliance to the relatively toxic antimalarial drugs. While drug toxicity and poor pharmacological potentials have been addressed or ameliorated with various nanomedicine drug delivery systems in diseases like cancer, no clinically significant success story has been reported for malaria. There have been several reviews on the application of nanomedicine technologies, especially drug encapsulation, to malaria treatment. Here we extend the scope of the collation of the nanomedicine research literature to polymer therapeutics technology. We first discuss the history of the disease and how a flurry of scientific breakthroughs in the latter part of the nineteenth century provided scientific understanding of the disease. This is followed by a review of the disease biology and the major antimalarial chemotherapy. The achievements of nanomedicine in cancer and other infectious diseases are discussed to draw parallels with malaria. A review of the current state of the research into malaria nanomedicines, both encapsulation and polymer therapeutics polymer-drug conjugation technologies, is covered and we conclude with a consideration of the opportunities and challenges offered by both technologies.

Promising nanomaterials in the fight against malaria

“…20 Like other 8-aminoquinoline-type drugs, primaquine can entail risk for patients with glucose-6-phosphate dehydrogenase deficiency, which is unfortunately very common in malariaendemic areas. 24 On the other hand, ATS, artemether, arteether and dihydroartemisinin are the most common artemisinin derivatives employed to treat malaria through artemisinin-based combination therapy (ACT). 21 The most frequent ACT drug combinations to treat uncomplicated malaria are artemether/lumefantrine, ATS/ amodiaquine, dihydroartemisinin/piperaquine, ATS/mefloquine and ATS/sulfadoxine-pyrimethamine.…”

“…108 Generally, an enzyme or pH-sensitive linker is employed to enable drug release once in the intracellular environment. 24 Despite the scarce exploration of this strategy in the field of infectious diseases caused by a parasite, its successful use for leishmaniasis treatment 109,110 encouraged its application to malaria since both pathologies share many features. 24 PQ represents the most widely studied antimalarial drug within the polymer-drug conjugation approach.…”

Porphyrin Derivative Nanoformulations for Therapy and Antiparasitic Agents

“…Nanoformulations have also been investigated for malaria treatment. For this purpose, the activity of conventional antimalarial drugs has been enhanced, especially by encapsulation in liposomes, micelles, polymeric particles, cyclodextrin, and dendrimers [137][138][139][140][141][142]. The first work on the incorporation of traditional antimalarial drugs into liposomes was published in 1989 by Peeters et al [143,144].…”

In vitro and in vivo antimalarial activity of Nigella sativa L. extracts

“…Chemotherapy plays a crucial role in malaria control (Mvango et al, 2018). Effective antimalarial drug should have therapeutic activity and no toxicity on human host (Na-Bangchang and Karbwang, 2009).…”