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.
Modified chitosan was prepared by chemical derivatisation using caproyl and palmitoyl fatty acid chains. The performance of the materials on the removal of phosphates in aqueous solutions was evaluated through a series of batch adsorption experiments. The phosphate adsorption studies showed enhanced adsorption efficiencies for caproyl chitosan (63%) and for palmitoyl chitosan (71%) in aqueous solutions containing phosphate at a pH of 6.2. The pristine and modified chitosans showed increases in the removal efficiency at an optimal solution pH of 4. The adsorption kinetics studies performed on palmitoyl-chitosan indicated that a contact time of approximately 30 minutes is required to reach equilibrium at solution concentrations ranging from 10-20 mg/l. Co-existing anions such as nitrates and sulphates do affect the phosphate removal efficiency of modified chitosans in aqueous solutions. This study demonstrates that modified chitosans has the potential of being used as a rigid and degradable material for water treatment.
Uncomplicated malaria is effectively treated with oral artemisinin‐based combination therapy (ACT). Yet, there is an unmet clinical need for the intravenous treatment of the more fatal severe malaria. There is no combination intravenous therapy for uncomplicated due to the nonavailability of a water‐soluble partner drug for the artemisinin, artesunate. The currently available treatment is a two‐part regimen split into an intravenous artesunate followed by the conventional oral ACT . In a novel application of polymer therapeutics, the aqueous insoluble antimalarial lumefantrine is conjugated to a carrier polymer to create a new water‐soluble chemical entity suitable for intravenous administration in a clinically relevant formulation . The conjugate is characterized by spectroscopic and analytical techniques, and the aqueous solubility of lumefantrine is determined to have increased by three orders of magnitude. Pharmacokinetic studies in mice indicate that there is a significant plasma release of lumefantrine and production its metabolite desbutyl‐lumefantrine (area under the curve of metabolite is ≈10% that of the parent). In a Plasmodium falciparum malaria mouse model, parasitemia clearance is 50% higher than that of reference unconjugated lumefantrine. The polymer‐lumefantrine shows potential for entering the clinic to meet the need for a one‐course combination treatment for severe malaria.
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