Human African trypanosomiasis (HAT), also commonly known as sleeping sickness, is a\nneglected tropical disease affecting millions of people in poorly developed regions in sub-Saharan\nAfrica. There is no satisfactory treatment for this infection. The investment necessary to bring new\ndrugs to the market is a big deterrent to drug development, considering that the affected communities\nform a non-lucrative sector. However, natural products and many sesquiterpene lactones (STLs) in\nparticular are very strong trypanocides. Research and applications of nano-drug delivery systems\nsuch as nanoparticles (NPs) have undergone unprecedented growth in the recent past. This is\nmainly due to the advantages offered by these systems, such as targeted delivery of the drug to\nthe place of action (cell, parasite, etc), sustained release of the drug, increased bioavailability,\nreduced drug dosage, and reduction of undesired side effects, among others. In this study,\nthe STLs alpha-santonin, arglabin, schkuhrin II, vernolepin, and eucannabinolide, all trypanocides,\nwere loaded into polylactic acid (PLA) NPs through an emulsification-diffusion method. The NPs\nwere stable, homogenous, and spherical in shape with a rounded knotty depression like a navel\norange. The average particle sizes were 202.3, 220.3, 219.5, 216.9, and 226.4 nm for alpha-santonin,\narglabin, schkuhrin II, vernolepin, and eucannabinolide, respectively. The NPs had encapsulation\nefficiencies of 94.6, 78.1, 76.8, 60.7, and 78.9% for Alpha-santonin, arglabin, schkuhrin II, vernolepin,\nand eucannabinolide, respectively. The NPs loaded with arglabin, vernolepin, and eucannabinolide\nexhibited considerable antitrypanosomal activity against Trypanosoma brucei rhodesiense (Tbr) with\nfree drug equivalent IC50 values of 3.67, 1.11 and 3.32 microM, respectively. None of the NP formulations\ndisplayed cytotoxicity towards mammalian cells (rat skeletal myoblast cell line L6). These results\nprovide new insights into the possibility of incorporating STLs into nanoparticles, which may provide\nnew options for their formulation in order to develop new drugs against HAT.
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