Trypanosomiasis is a parasitic infection caused by Trypanosoma. It is one of the major causes of deaths in underprivileged, rural areas of Africa, America and Asia. Depending on the parasite species responsible for the disease, it can take two forms namely African trypanosomiasis (sleeping sickness) and American trypanosomiasis (Chagas disease). The complete life-cycle stages of trypanosomes span between insect vector (tsetse fly, triatomine bug) and mammalian host (humans, animals). Only few drugs have been approved for the treatment of trypanosomiasis. Moreover, current trypanocidal therapy has major limitations of poor efficacy, serious side effects and drug resistance. Due to the lack of economic gains from tropical parasitic infection, it has always been neglected by the researchers and drug manufacturers. There is an immense need of more effective innovative strategies to decrease the deaths associated with this diseases. Nanotechnological approaches for delivery of existing drugs have shown significant improvement in efficacy with many-fold decrease in their dose. The review emphasizes on nanotechnological interventions in the treatment of trypanosomiasis in both humans and animals. Current trypanocidal therapy and their limitations have also been discussed briefly.
The objective of the present study was to develop long-acting efavirenz (Efa)−enfuvirtide (Enf) Co-loaded polymer−lipid hybrid nanoparticles (PLN) with improved intracellular delivery to target T-cells and macrophage cells located in multiple human immunodeficiency virus sanctuaries. The Box−Behnken design was utilized to optimize three high-risk factors, namely, Efa amount, sonication time for primary emulsion, and sonication time for aqueous nanodispersion obtained from preliminary studies. Lyophilized Efa−Enf Co-loaded PLN using trehalose elicited spherical morphology, drug amorphization on incorporation, and absence of drugexcipient interaction. In vitro release studies revealed an sustained release of both the drugs from PLN with the differential release profile. Efa−Enf Coloaded PLN exhibited low hemolytic, platelet and leukocyte aggregation as well as low cytotoxicity in Jurkat E6.1 T-cells and U937 macrophage cells. Circular dichroism spectra confirmed the presence of an α-helix form of Enf after encapsulation in PLN. Coumarin-6-loaded PLN exhibited enhanced cellular uptake in Jurkat E6.1 T-cells and U937 macrophage cells in comparison to free coumarin-6, as evidenced by fluorescence microscopy and flow cytometry. In vivo biodistribution studies after intravenous administration of near-infrared dye-loaded PLN (surrogate for Efa−Enf PLN) revealed non-uniform distribution within 2 h in the order of spleen ≥ liver > lymph node > thymus > lungs > female reproductive tract (FRT) > heart > kidneys > brain. However, subcutaneous administration caused non-uniform biodistribution after 3 days, eliciting a long-acting slow release from the injection site depot until day 5 in the infection-spread site (lymph nodes and FRT), reservoir sites (liver and spleen) and the difficult-to-access site (brain). Furthermore, it presents a vital illustration of the available tissue-specific drug concentration prediction from simulated surrogate PLN.
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.