Nanotechnology based solutions for anti-leishmanial impediments: a detailed insight

Abstract

As a neglected tropical disease, Leishmaniasis is significantly instigating morbidity and mortality across the globe. Its clinical spectrum varies from ulcerative cutaneous lesions to systemic immersion causing hyperthermic hepato-splenomegaly. Curbing leishmanial parasite is toughly attributable to the myriad obstacles in existing chemotherapy and immunization. Since the 1990s, extensive research has been conducted for ameliorating disease prognosis, by resolving certain obstacles of conventional therapeutics viz. poor efficacy, systemic toxicity, inadequate drug accumulation inside the macrophage, scarce antigenic presentation to body’s immune cells, protracted length and cost of the treatment. Mentioned hurdles can be restricted by designing nano-drug delivery system (nano-DDS) of extant anti-leishmanials, phyto-nano-DDS, surface modified—mannosylated and thiolated nano-DDS. Likewise, antigen delivery with co-transportation of suitable adjuvants would be achievable through nano-vaccines. In the past decade, researchers have engineered nano-DDS to improve the safety profile of existing drugs by restricting their release parameters. Polymerically-derived nano-DDS were found as a suitable option for oral delivery as well as SLNs due to pharmacokinetic re-modeling of drugs. Mannosylated nano-DDS have upgraded macrophage internalizing of nanosystem and the entrapped drug, provided with minimal toxicity. Cutaneous Leishmaniasis (CL) was tackling by the utilization of nano-DDS designed for topical delivery including niosomes, liposomes, and transfersomes. Transfersomes, however, appears to be superior for this purpose. The nanotechnology-based solution to prevent parasitic resistance is the use of Thiolated drug-loaded and multiple drugs loaded nano-DDS. These surfaces amended nano-DDS possess augmented IC50 values in comparison to conventional drugs and un-modified nano-DDS. Phyto-nano-DDS, another obscure horizon, have also been evaluated for their anti-leishmanial response, however, more intense assessment is a prerequisite. Impoverished Cytotoxic T-cells response followed by Leishmanial antigen proteins delivery have also been vanquished using nano-adjuvants. The eminence of nano-DDS for curtailment of anti-leishmanial chemotherapy and immunization associated challenges are extensively summed up in this review. This expedited approach is ameliorating the Leishmaniasis management successfully. Alongside, total to partial eradication of this disease can be sought along with associated co-morbidities.

Preclinical Assessment of Ursolic Acid Loaded into Nanostructured Lipid Carriers in Experimental Visceral Leishmaniasis

“…In animals treated with UA-NLC or AmB, a focal inflammatory process was observed, and it was characterized by a discrete infiltration of mononuclear cells in the portal space with low parasitism. The increased leishmanicidal activity and reduced inflammatory process observed in the spleen and liver of animals treated with UA-NLCs in comparison with animals treated with UA can be associated with the uptake of nanoparticles by macrophages, destruction of amastigote forms and the inhibition of inflammation as the number of parasites drastically decreased in the spleen and liver [63]. These data suggest that treatment performed with UA-NLCs preserved the histology of the liver and spleen, since the animals displayed small areas of inflammation in these organs and developed a potent immune response compared to animals treated with UA and nontreated infected groups.…”

Leishmania 360°: Guidelines for Exosomal Research

“…The authors also conclude that physicochemical stimuli may play an important role in the content and function of isolated extracellular vesicles [8]. Despite all these considerations, the research has, in general, focused primarily on the description of the different clinical forms of LEV, in particular, in the visceral strains and in the proteomics of L. (L.) mexicana under the same conditions, which has provided valuable information on how polymorphisms in the LEV proteins may affect the cell-to-cell interactions between parasites and the host-parasite or the leishmanicidal activity [4,12,14,35,124]. Even so, comparative analyses of the reproducible isolation and the description of LEVs from procyclic and metacyclic-like in vitro cultures of a wider range of Leishmania species are still scarce [76,116,122].…”

“…In mammals, persistent Leishmania infection is linked with macrophage signaling pathways that block microbicidal functions and the innate response of the host during infection [14]. In this case, the LEVs are effectively macrophage immunomodulators of early host inflammatory responses, although the exact mechanisms involved in this process are yet to be fully understood [6,12,35,85,117]. The immune response is a critical aspect of the infection process and the establishment of the disease through the development of protective immunity associated with the intracellular destruction of the amastigotes by the macrophages, which will depend, in turn, on the induction of an efficient cellular response through the production of cytokines such as IFNγ, interleukins (IL), and TNF-α [20].…”

“…This ability to infect multiple species has facilitated the spread of Leishmania worldwide, and despite the development of some veterinary vaccines, the lack of effective vaccines and drug treatments for humans has allowed the rate of infections to continue to increase [8][9][10][11]. Promising new technology, including nanotechnological approaches, have developed over the past few decades to improve the prevention of leishmaniasis, the detection of the parasite, and its treatment [8,[11][12][13]. The importance of the extracellular vesicles has stimulated considerable interest in the scientific community, given their apparent potential for the development of effective diagnostic and therapeutic approaches, including the prediction of the outcome of the interaction between cells [14][15][16][17].…”

Development, Characterization, and Evaluation of SLN-Loaded Thermoresponsive Hydrogel System of Topotecan as Biological Macromolecule for Colorectal Delivery

“…Similarly, SLNs are reported to protect incorporated drug and offer controlled release of the drug in vivo [ 11 – 13 ]. An SLN-based nanocarrier system has the capability to abridge some of the drawbacks of traditional anticancer therapies, including lack of selectivity, induced tissue toxicity, reduced uptake by tumour cells, and instability [ 14 – 16 ]. Although being very effective for drug delivery, the SLNs sometimes demonstrate the burst release of its incorporated drugs leading to severe toxicity and failure of the therapy [ 17 , 18 ].…”