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.
Drug delivery systems involving polymer therapeutics enhance drug potency by improved solubility and specificity and may assist in circumventing chemoresistance in pancreatic cancer (PC). We compared the effectiveness of the naturally occurring drug, betulinic acid (BA), alone and in a polymer conjugate construct of polyethylene glycol (PEG), (PEG–BA), on PC cells (MIA PaCa-2), a normal cell line (Vero) and on peripheral blood mononuclear cells (PBMCs). PEG–BA, was tested for its effect on cell death, immunomodulation and chemoresistance-linked signalling pathways. The conjugate was significantly more toxic to PC cells (p < 0.001, IC50 of 1.35 ± 0.11 µM) compared to BA (IC50 of 12.70 ± 0.34 µM), with a selectivity index (SI) of 7.28 compared to 1.4 in Vero cells. Cytotoxicity was confirmed by increased apoptotic cell death. PEG–BA inhibited the production of IL-6 by 4–5.5 fold compared to BA-treated cells. Furthermore, PEG–BA treatment of MIA PaCa-2 cells resulted in the dysregulation of crucial chemoresistance genes such as WNT3A, TXNRD1, SLC2A1 and GATA3. The dysregulation of chemoresistance-associated genes and the inhibition of cytokines such as IL-6 by the model polymer construct, PEG–BA, holds promise for further exploration in PC treatment.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.