Visceral leishmaniasis is a parasitic disease found in tropical and subtropical regions and is life threatening because there is no vaccination for prevention (Y. Want, et al., 2017: pg. 2189). In addition, treatment options are mostly ineffective or dangerous (Y. Want, et al., 2017: pg. 2189). One treatment, artemisinin, is highly effective against visceral leishmaniasis but has previously been considered one of the most dangerous treatment options due to its physicochemical properties (Y. Want, et al., 2017: pg. 2189). However, it has been recently discovered that artemisinin can be safely administered when incorporated with colloidal nanoparticles (Y. Want, et al., 2017: pg. 2189).
There are great expectations for the use of the liposomal drug delivery method in the medical management of infectious diseases, and it has been implemented previously in clinical practice (Y. Want, et al., 2017: pg. 2190). However, prior to this study, the use of nanoliposomal artemisinin has not be used in the treatment of visceral leishmaniasis (Y. Want, et al., 2017: pg. 2190). According to projections, there is great potential for using nanoliposomal artemisinin as the main treatment for this infectious disease, and it would seem that the incorporation of liposomes will not only mitigate the dangerous side effects of artemisinin, but will also increase its efficacy against visceral leishmaniasis (Y. Want, et al., 2017: pg. 2190).
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In order to proceed with the drug testing, parasites of the AG83 strain of leishmaniasis were isolated and used to infect the murine subjects (Y. Want, et al., 2017: pg. 2190). Both female mice and golden hamsters were used as test subjects, and the nanoliposomal artemisinin was prepared using a three factor, three level Box-Behnken design (Y. Want, et al., 2017: pg. 2190). The nanoliposomal artemisinin was optimized by using ANOVA in Design Expert® and the independent factors were chosen based on optimal desirability criteria, such as minimum particle distribution, minimum particle size, maximum drug loading, and maximum stability (Y. Want, et al., 2017: pg. 2191).
Using dynamic light scattering, the mean particle size distribution, particle diameter, and zeta potential were determined, and the samples were reconstituted in preparation (Y. Want, et al., 2017: pg. 2191). Drug loading of the nanoliposomes was carefully determined using DMSO disruption of the liposomes (Y. Want, et al., 2017: pg. 2191). Storage stability was careful calculated and optimized, followed by the determination of cytotoxicity and in vivo toxicity (Y. Want, et al., 2017: pg. 2192). After the completion of these steps, the in vivo infection and treatment began, followed by the determination of Leishmania specific antibodies (Y. Want, et al., 2017: pg. 2193). Seventeen combinations of nanoliposomal artemisinin were generated overall, with 72 – 138 nm particle size, -22 mv to -37 mv zeta potiental, and a PDI between 0.20 and 0.39 (Y. Want, et al., 2017: pg. 2193). During the study period, there were no factors that flagged a reason to be concerned about the storage stability of the nanoliposomal artemisinin (Y. Want, et al., 2017: pg. 2193). The drug released from of the nanoliposomes was not affected by the pH of the medium used for drug delivery (Y. Want, et al., 2017: pg. 2194).
The nanoliposomes were a success in that they showed no signs of nephro- or hepatotoxicity (Y. Want, et al., 2017: pg. 2194). The nanoliposomal artemisinin also had improved efficacy against the leishmaniasis infected macrophages (Y. Want, et al., 2017: pg. 2195). The nanoliposomal artemisinin caused a decrease in parasite burden and the subjects treated with the nanoliposomal artemisinin showed a restoration of cellular immunity (Y. Want, et al., 2017: pg. 2197). Visceral leishmaniasis suppresses T-cell response as part of its pathogenesis, and this impairment was successfully removed by the treatment of nanoliposomal artemisinin (Y. Want, et al., 2017: pg. 2197). Progression of visceral leishmaniasis is heavily reliant on the inducement of Th 2 cytokine production, but this can be countered with an increase in Th 1 secretions (Y. Want, et al., 2017: pg. 2197) There was also clear evidence that the immune response was modulated efficiently by the nanoliposomal artemisinin, and it was pivotal in the removal of Leishmania intracellularity (Y. Want, et al., 2017: pg. 2198). In addition, the secretion of TH 1 was reinforced by the nanoliposomal artemisinin, which was evidenced by positive lymphoproliferation (Y. Want, et al., 2017: pg. 2198).
Prior to nanoliposomal artemisinin, the treatment for visceral leishmaniasis was limited and ineffective at its best, and dangerous at its worst. The study carefully laid out the planning of the infecting the subjects and how the nanoliposomal artemisinin would be created. Care was taken with the delivery of the experiment, ensuring that all protocols were followed.
Nanoliposomal artemisinin showed positive results in ridding the subjects of the visceral leishmaniasis without compromising the health of the subject. In the future, the nanoliposomal artemisinin looks to be a promising treatment for this life-threatening ailment. However, this study was performed on animal subjects, so further testing on the human immune system will be necessary to ensure efficacy and safety. In light of the danger and inefficiency of the current treatments, the promising results of this study should be quickly followed up on to ensure that life is not unnecessarily lost. It would also be worth scientific inquiry for the nanoliposomal technique be explored with other medications that could benefit from a safer delivery method, and/or a reduction of dangerous side effects.
- Y. Want, Muzamil et al. “Nanoliposomal Artemisinin For The Treatment Of Murine Visceral Leishmaniasis”. International Journal of Nanomedicine Volume 12 (2017): 2189-2204. Web.
