Open access peer-reviewed chapter

Plant-Based Alternative Treatment for Leishmaniasis: A Neglected Tropical Disease

Written By

Nargis Shaheen, Chaitenya Verma and Naveeda Akhter Qureshi

Submitted: August 1st, 2021 Reviewed: December 9th, 2021 Published: April 13th, 2022

DOI: 10.5772/intechopen.101958

Chapter metrics overview

23 Chapter Downloads

View Full Metrics

Abstract

Leishmaniasis is a third most important vector born disease caused by intracellular parasite belongs to genus Leishmania. The leishmaniasis is prevalent in 102 countries/areas worldwide. Approximately, it effected 350 million people worldwide. Leishmaniasis effects developing and undeveloped countries globally. Antileishmanial drugs (pentavalent antimonials, stibogluconate, miltefosine, paramycin, and amphotericin) are most vital tool for curing leishmaniasis. However, none of these drugs is free from side effect including cost, toxicity, drug resistance, administration route, and prolong time, these disadvantages are main obstacle in the Leishmania infection eradication. Considering the increasing cases of leishmaniasis and drug resistance there is an urgent need for an effective and novel approach against leishmaniasis. Therefore, many researchers have tried to develop new medicines for the treatment of Leishmania infection. In the course of new therapies identification, plant based compounds were found to be an alternative that can be either used directly or with structural modifications. Several plants have been known for ages to be the source of phytochemicals with high values of medicines. These phytochemicals have been extracted by various techniques and have shown efficacy for the curing of several diseases. This chapter study explain various applications based on green approaches drugs for the treatment of leishmaniasis.

Keywords

  • leishmaniasis
  • treatment
  • nanoparticles
  • alternative
  • green approach

1. Introduction

1.1 Leishmaniasis

The neglected tropical diseases (NTDs) are a group of about 17 parasitic diseases. The NTDs are prevalent in many tropical and subtropical countries that present the most common illness of the poorest people worldwide [1]. Leishmaniainfection constitutes a foremost public health issue with a rising burden over the last decade and is the second main cause of disease and death [2]. Leishmaniasis is prevalent in 102 countries/areas worldwide [3]. Leishmaniainfection affects approximately 1.5–2 million people, while 350 million are at risk of this pathogen [4, 5]. The causative agent of leishmaniasis is parasite protozoa of the genus Leishmaniaand is transferred via vector sandfly bite belongs to genus Lutzomyiaand Phlebotomus[6].

Three clinical forms of leishmaniasis have been reported concerning parasite location in the infected tissues, that is, visceral leishmaniasis (VL) which is a less common type of leishmaniasis and it causes spleen and liver destruction and causes death if does not receive timely treatment; cutaneous leishmaniasis (CL), which affect only localized skin parts; and mucocutaneous leishmaniasis (MCL), which has the ability of mucus tissue destruction [7, 8]. About 0.7–1.2 million CL and 0.2–0.4 million VL cases are reported annually. Approximately CL cases (90%) are spread across three main areas, that is, (a) Syria, Afghanistan, Saudi Arabia, and Iran; (b) Tunisia and Algeria; and (c) Peru and Brazil [9, 10]. Annual visceral leishmaniasis (VL) cases are estimated to be less than 100,000, down from 400,000 in previous estimates [11], with more than 95% of cases reported to the World Health Organization (WHO) from Brazil, China, Ethiopia, India, Kenya, Nepal, Somalia, and Sudan. Currently, 54 Leishmaniaspp. are known and twenty-one are human’s pathogenic [8].

Advertisement

2. Therapeutic approaches and their limitations

Leishmaniasis is one of the most common NTDs, and it comes with a slew of negative and life-threatening consequences, including significant morbidity, early death, and long-term disability. Treatment entails limiting illness spread and utilizing existing criteria, but present medicines, such as chemical pharmaceuticals, need long-term treatment, minimal efficacy, and a slew of hazardous side effects. Only a few prevention strategies are available, despite the fact that no appropriate medications have been produced to prevent the virus, which is widely transmitted among the human population [12]. Some clinically approved medications are discovered among them to treat this endemic condition, that is, meglumine antimoniate (glucatime), sodium stibogluconate (pentostan), amphotericin B, and miltefosine. Excessive use of these chemotherapeutic sources, on the other hand, has been linked to antagonistic consequences [13]. As a result, researchers are looking for natural ways to treat leishmaniasis. Leishmaniasis treatment using chemical-based drugs various pharmacological medications, such as amphotericin B, pentamidine, miltefosine, and paromomycin, have been used in the treatment of leishmaniasis for numerous years. Due to the time-consuming method and high toxicity paired with significant adverse effects, none of the clinically approved medications could be considered as the ultimate source of treatment. Furthermore, the most commonly used medications do not completely eliminate parasites from all afflicted individuals [14]. The applications of several of these drugs, as well as their drawbacks, are explained further below. Pentavalent antimonials can be given via intravenous, intramuscular, and intralymphatic methods, with an optimum dose of 20 mg/kg/day (28–30 days) and a potentiality of 35–95%. This medicine can cause toxicity such as nephrotoxicity, hepatotoxicity, severe cardiotoxicity, and pancreatitis if used excessively [12, 13]. Miltefosine, when given orally, had an inhibitory effect on Leishmaniagrowth but also had a negative effect, causing severe infection symptoms such as nephrotoxicity, teratogenicity, vomiting and diarrhea, and hepatotoxicity [15]. Paromomycin, which is also used to treat leishmaniasis, has been documented to have several hazardous side effects during treatment, including severe nephrotoxicity, hepatotoxicity, and ototoxicity [16]. Pentamidine, at a starting dose of 3 mg/kg/day, has the potential to slow Leishmaniadevelopment while also causing significant side effects including as hypotension, hyperglycemia, tachycardia, pancreatic damage, and electrocardiographic abnormalities changes [14]. Existing chemotherapies have a number of drawbacks, including high cost, increased toxicity, and acquired resistance to parasitic strains, as well as other side effects during their prevention mechanism, prompting scientists and medical practitioners to develop a new therapeutic system to treat NTDs. Plant extracts, bioactive chemicals, and secondary metabolites obtained from specific plant species, as well as various types of NPs manufactured using plant extract, have become promising as well as safer preventative medicines in recent decades.

Advertisement

3. Natural methods

Plant-based conventional treatments have been employed in the treatment of infectious diseases since ancient times. Plant extracts and specific bioactive compounds isolated from plants are currently employed as either direct medicinal sources or as herbal medications to treat leishmaniasis and other microbiological infections [17]. Due to their nontoxic, environmentally friendly, and cost-effective features, medicinal plants become more favorable than other chemotherapies. Furthermore, natural chemicals derived from plants are regarded as a safe and effective treatment for leishmaniasis [18].

The root extract Bidens pilosahas been reported for antileishmanial potential against promastigotes of L. amazonensiswith IC = 1.5 μg/ml). The Eugenia unifloraoil inhibit the growth of promastigotes and amastigotes of L. amazonensiswhile Ageratum conyzoideshas been active against amastigots form of Labrus donovani[19]. The component of Casearia sylvestrisand Melampodium divaricatumhas been reported against L. amazonensiswith IC50 = 10.7 and 14.0 μg/ml [20]. Furthermore, the active components 1,8-cineole, -pinene, and p-cymene from Protium altsoniiand P. hebetatum(Burseraceae) showed dose-dependent amastigote inhibition, with IC50 values of 48.4, 37, and 46 g/ml, respectively [21]. The butanol fraction of K. odoratissimadisplayed antileishmanial activities against L. majorpromastigote and amastigote with an IC50 value of 154.1 g/ml [22].

Advertisement

4. Role of plant-based nanoparticles in leishmaniasis treatment

Infectious illness control methods have revolutionized translational sciences, allowing for the development of a better infectious disease control approach. Nanomedicine has showed tremendous promise in the development of very sensitive diagnostic tools with outstanding medication delivery properties. Nanoparticle-conjugated medications have recently been examined as a cost-effective, alternative therapy with improved efficacy. Toxicity, on the other hand, is a significant impediment that must be overcome. Several studies have demonstrated that several metal/metal oxide nanoparticles, as well as the Leishmaniacausative organism, have effective antibacterial effects due to their large surface area and unique characteristics. Nanoparticles made from crude and various solvent-fractionated extracts of medically significant plants are thought to be effective delivery for specific phytoconstituents into cells. Keeping in view the effective antimicrobial activities of silver metal, silver/silver oxide NPs synthesized using a variety of medicinally important plant species, including Mentha arvensisL., Ficus benghalensis, Cuminum cyminum, Moringa oleifera, Silybum marianum, and Sechium edule, at a dosage of 10, 300, 0.5, 246, and 51.88 μg/ml tested against L. tropica, L. donovani, L. major, and L. donovani, respectively [23, 24, 25, 26, 27]. This condition has also been reported to be prevented utilizing gold and silver bimetallic NPs produced from therapeutically significant plants [28]. However, Au-NPs derived from Cannabis sativahad excellent antileishmanial activity against amastigote forms (IC50: 171•00± 2•28 μg/ml) [25]. The flavonoid 7,8-dihydroxyflavone, which is common in plants used to make gold nanoparticles, has also been shown to prevent leishmaniasis [29]. The cytotoxicity of ZnO-NPs against L. tropicawas likewise observed to be dose-dependent (IC50: 8.30 μg/ml). With an IC50 value of 0.001 mg ml, rod-shaped zinc oxide NPs made from Lilium ledebouriituber extract suppressed the growth of L. major[29]. Saleh [30] also found that green TiO2 nanoparticles were efficient in reducing L. tropicatoxicity in male rats. Hematite (Fe2O3) NPs made from Rhus punjabensisextract were found to be effective in the treatment of leishmaniasis [31]. Khalil et al. [32] used aqueous leaf extracts of Sageretia theato make lead oxide NPs (PbO-NPs). PbO-NPs were found to be significantly active in stopping the growth of promastigote and amastigotes forms of L. tropica, with IC50 values of 14.7 and 11.95 g/ml, respectively. Plant-mediated iron oxide nanoparticles (Trigonella foenum-graecum) have been shown to have considerable inhibitory effects on L. tropica[33]. Abbasi et al. [34] also indicated that NiO-NPs made from Geranium wallichianumhas antileishmanial activity against L. tropica.

In addition, the nanostructured drug delivery method has been shown to help with NTDs like leishmaniasis. Furthermore, crude plant extracts and specific phytoconstituents produced from plants that are involved in the preventative mechanism were loaded into the nanostructured drug delivery system and used as a therapeutic source to cure leishmaniasis, as shown below:

  • Liposome NPs containing phospholipids are used as a transport system for the delivery of both hydrophilic and lipophilic medicinal medicines [35]. They give superior pharmacokinetic assets as well as target diligence, which is a significant benefit [36]. Through phagocytosis, liposomes can spear macrophages and transport medications directly to their target areas. Various medication formulations, such as AmB colloidal formulations, liposomal AmB, and the AmB lipid network, can significantly reduce the toxicity of traditional pharmaceuticals [20].

  • Antileishmanial effects of liposome-encapsulated Curcuma longaand Combretum leprosumextracts have also been discovered [37, 38].

  • The usage of beta-lapachone isolated from the Lapacho tree and encapsulated with lecithin-chitosan NP has been described in the treatment of leishmaniasis [20].

  • Leishmaniahas been treated with 8-hydroxyquinoline encapsulated in polymeric micelles [39]. Berberin is an isoquinoline alkaloid derived from medicinal plants that has been shown to have a variety of biologic features, including antileishmanial activity. In VL, a prior study focused on the development of BER-loaded liposomes with the goal of preventing rapid liver metabolism and improving drug selective delivery to diseased organs [40].

According to the literature review, plant-based nanoparticles play an effective function in the treatment of leishmaniasis when compared to other treatments. At a far lower concentration than the required dose of Amp B to cure this condition, phytosynthesized NPs had the same effect on parasite growth suppression. Furthermore, green bimetallic nanoparticles such as Au-Ag, Zn-Ag, and Ti-Ag were produced and successfully used as a medicinal source to treat leishmaniasis [28]. Because of its nontoxic, safe, and efficient vaccine delivery technique, NPs are recommended above other medicinal options to treat this dreadful disease. With the progress of nanosciences, a new way of producing vaccines employing NPs as antigen carriers is now available. Solid lipid nanoparticles may be useful in the development of a leishmanial vaccine [41]. However, no NP-based vaccination is currently available, and further research is required.

Advertisement

5. Restorative mechanism of nanoformulations against leishmaniasis

The protozoan parasite Leishmaniaspp. causes cutaneous and visceral leishmaniasis. Depending on the immune responses induced by the diseased host, several clinical investigations show the development of self-curable to adverse situations [42]. Pentavalent antimonials (such as sodium stibogluconate or meglumine antimoniate) and other antileishmanial medications (amphotericin B, fluconazole, pentamidine, and miltefosine) are the most effective treatments for leishmaniasis. However, undesirable effects, high costs, complicated infusion routes, low cure rates, and rising resistance are all major concerns when it comes to developing more effective leishmaniasis treatments. Furthermore, the efficacy of the medicine employed in treatment differs per leishmanial species [28, 40, 42]. In self-treatment, phagocytes recognize and devour the causative agents, causing Leishmaniaassassination by releasing reactive oxygen species, nitric oxide, and tumor necrosis factors [43]. Following innate immune responses, TH1 immunity activates and produces CD8+, NK, and IFN cells, which kills the Leishmaniaparasites [42]. In sensitive situations, the defense system fails to overcome infections, resulting in erroneous TH2 immune responses as well as antibody responses, which is the main factor in developing new parasite elimination methods. Infected cells’ proliferation and viability are inhibited by metal nanoparticles, which is dependent on the NP strength and exposure period [44, 45]. Several in vitro and in vivo data imply that bio-Ag-NPs have leishmanicidal actions via direct (non-inflammatory) or indirect (immunomodulatory) mechanisms [40, 45]. Metal-NPs destroy parasitic cells directly by producing vacuolation within the parasites and disruption to the cellular membrane, without generating immunomodulatory intermediaries such as reactive oxygen species (ROS), nitric oxide (NO), and apoptotic and necrotic factors [45]. Nanoformulations aid site-specific delivery and accumulation of medicines, which is responsible for parasite killing, when Leishmaniaparasites override the oxidative burst inside phagocytic cells and dwell in phagolysosomes [46]. According to Fanti et al. (2018) [45], Ag-NPs are oxidized by acidic conditions within the phagolysosomes following passage through the cellular membranes, and the release of free Ag + ions induces parasite assassination. The indirect strategy, on the other hand, includes inducing immunomodulatory responses at infection sites. Other methods of providing leishmanicidal effects include activating immune response mediators and reducing cell viability and proliferation as a result of metallic nanoparticles. NPs cause a variety of morphological changes, including distorted membrane integrity, cytotoxicity, mitochondrial destruction, cell cycle arrest (G1), increased/decreased ROS and NO production, altered enzymatic activity, and the release of apoptotic or necrotic components [47, 48, 49]. As a result of mitochondrial disintegration, ATP production is harmed, which leads to cytotoxic effects and, in turn, impairs infection growth [50]. Furthermore, NP exposure results in a lower parasitic load and a decrease in the trypanothione reductase system, which is an important parasitic enzyme [45].

Advertisement

6. Conclusions

Chemotherapy has become the only option for treating leishmaniasis due to a lack of effective medicines. However, these medications have increased degrees of toxicity, treatment costs, and resistance development against leishmanial parasites, as well as other side effects. Furthermore, due to leishmanial antigen variations and varied immunological responses to the treatment, the efficacy of medicines differs from species to species. Biogenic nanomaterials have been suggested as helpful alternatives to formulate nanovaccines since they are nontoxic, biocompatible, cost effective, and have high targeted drug-loading potentials. Nanoformulations can be used to overcome targeted medication transport hurdles, resulting in increased parasiticidal efficacy. Moreover, plant-derived natural compounds (such as berberine, 7,8-dihydroxyflavone, E-caryophyllene, essential oil constituents, -terpineol, glycosides, tannins, and anthraquinone flavonoids) have been shown to have leishmanicidal activities in various studies, which can further integrate beneficial outcomes. Furthermore, the majority of leishmanicidal investigations revealed only the most basic results, such as determining the influence of test medications (crude extract, extracted bioactive components, essential oil, and purified fraction) on parasite growth. Few of them are able to determine the right formulation as well as the effect on the sandfly promastigote stage (vector). Plants include a range of bioactive chemicals, and the majority of them have been recognized for their medicinal qualities, according to the literature. As a result, standardization may lead to the identification of a specific component that has leishmanicidal properties. Biosynthesized nanoparticles mostly remove infection by triggering the host’s immunomodulatory response or, in rare cases, directly by causing parasitic cell vacuolization, resulting in parasite death. Nanovaccines are a relatively new concept in Leishmaniatreatment, and while no vaccine is currently available, research is ongoing to find effective nanovaccines. Although nanotechnology has given hope for better and more successful eradication of neglected tropical diseases, a complete understanding of the molecular mechanisms responsible is still needed.

Advertisement

Conflict of interest

None.

Advertisement

Notes/thanks/other declarations

All authors declare that they have no known competing financial interest or personal relationship that could have appeared to influence the work reported in this chapter.

References

  1. 1. World Health Organization (WHO). Control of the Leishmaniases. Report of a Meeting of the WHO Expert Committee on the Control of Leishmaniases. WHO/DOC/949. Geneva: WHO; 2010
  2. 2. Bern C, Maguire JH, Alvar J. Complexities of assessing the disease burden attributable to leishmaniasis. PLoS Neglected Tropical Diseases. 2008;2(10):313
  3. 3. Uzun S, Gürel MS, Durdu M, Akyol M, Karaman FB, Aksoy M, et al. Clinical practice guidelines for the diagnosis and treatment of cutaneous leishmaniasis in Turkey. International Journal of Dermatology. 2018;57(8):973-982
  4. 4. Souza A, Marins DSS, Mathias SL, Monteiro LM, Yukuyama MN, Scarim CB, et al. Promising nanotherapy in treating leishmaniasis. International Journal of Pharmaceutics. 2018;547:421-431
  5. 5. World Health Organization. Noncommunicable Diseases Country Profiles 2018. Geneva: WHO; 2018
  6. 6. Kamhawi S, Modi GB, Pimenta PFP, Rowton E, Sacks DL. The vectorial competence ofPhlebotomus sergentiis specific forLeishmania tropicaand is controlled by species-specific, lipophosphoglycan-mediated midgut attachment. Parasitology. 2000;121(1):25-33
  7. 7. Bifeld E, Clos J. The genetics ofLeishmaniavirulence. Medical Microbiology and Immunology. 2015;204:619-634
  8. 8. Akhoundi M, Kuhls K, Cannet A, Votypka J, Marty P, Delaunay P, et al. A historical overview of the classification, evolution, and dispersion ofLeishmaniaparasites and sandflies. PLoS Neglected Tropical Diseases. 2016;10(3):e0004349
  9. 9. Alvar J, Vélez ID, Bern C, Herrero M, Desjeux P, Cano J. WHO Leishmaniasis Control Team. Leishmaniasis worldwide and global estimates of its incidence. PLoS One. 2012;7(5):e35671
  10. 10. Alvar J, Velez ID, Bern C. Leishmaniasis worldwide and global estimates of its incidence. PLoS One. 2012;7:356-371
  11. 11. CDC. Epidemiology and risk factors. Available from:https://www.cdc.gov/parasites/leishmaniasis/epi.html
  12. 12. Gharirvand Eskandari E, Setorki M, Doudi M. Medicinal plants with antileishmanial properties: A review study. Pharmaceutical and Biomedical Research. 2020;6(11):1-16
  13. 13. Ghobakhloo N, Motazedian MH, Fardaei M. Expression analysis of multiple genes may involve in antimony resistance amongLeishmania majorclinical isolates from Fars Province, Central Iran. Iranian Journal of Parasitology. 2016;11(2):168-176
  14. 14. De Menezes JPB, Guedes CES, Petersen ALdOA, Fraga DBM, Veras PST. Advances in development of new treatment for leishmaniasis. BioMed Research International. 2015;2015:1-11
  15. 15. Sundar S, Sinha PK, Rai M, Verma DK, Nawin K, Alam S, et al. Comparison of short-course multidrug treatment with standard therapy for visceral leishmaniasis in India: An open-label, non-inferiority, randomised controlled trial. Lancet. 2011;377(9764):477-486
  16. 16. Jhingran A, Chawla B, Saxena S, Barrett MP, Madhubala R. Paromomycin: Uptake and resistance inLeishmania donovani. Molecular and Biochemical Parasitology. 2009;164:111-117
  17. 17. Oryan A. Plant-derived compounds in treatment of leishmaniasis. Iranian Journal of Veterinary Research. 2015;16(1):1-19
  18. 18. Cheuka P, Mayoka G, Mutai P, Chibale K. The role of natural products in drug discovery and development against neglected tropical diseases. Molecules. 2017;22:58
  19. 19. Silveira ES, Castro Rodrigues NLD, Machado NJ, Marciano Fonseca FR, Teixeira MJ, Almeida Moreira Leal LK. Medicinal plants containing coumarin or essential oils from the Brazilian biome may be new option for treating leishmaniasis? Pharmacognosy Reviews. 2021;14:53-61
  20. 20. Moreira RRD, SantosDos AG, Carvalho FA, Perego CH, Crevelin EJ, Crotti AEM, et al. Antileishmanial activity ofMelampodium divaricatumandCasearia sylvestrisessential oils onLeishmania amazonensis. Revista do Instituto de Medicina Tropical de São Paulo. 2019;61:e33
  21. 21. Santana RC, Rosados ASS, Mateus MHS, Soares DC, Atella G, Guimaraes AC, et al.In vitroleishmanicidal activity of monoterpenes present in two species of protium (Burseraceae) onLeishmania amazonensis. Journal of Ethnopharmacology. 2020;259:112981
  22. 22. Mirzaei F, Norouzi R, Siyadatpanah A, Mitsuwan W, Nilforoushzadeh M, Maleksabet A, et al. Butanol fraction ofKelussia odoratissimaMozaff inhibits the growth ofLeishmania majorpromastigote and amastigote. Journal of World's Poultry Research. 2020;10:254-259
  23. 23. Baranwal A, Chiranjivi AK, Kumar A, Dubey VK, Chandra P. Design of commercially comparable nanotherapeutic agent against human disease-causing parasite,Leishmania. Scientific Reports. 2018;8:8814
  24. 24. Bagirova M, Dinparvar S, Allahverdiyev AM, Unal K, Abamor ES, Novruzova M. Investigation of antileshmanial activities ofCuminum cyminumbased green silver nanoparticles onL. tropicapromastigotes and amastigotesin vitro. Acta Tropica. 2020;208:105498
  25. 25. Hameed S, Ali Shah S, Iqbal J, Numan M, Muhammad W, Junaid M, et al. Cannabis sativa-mediated synthesis of gold nanoparticles and their biomedical properties. Bioinspired, Biomimetic and Nanobiomaterials. 2020;9:95-102
  26. 26. Javed B, Raja NI, Nadhman A, Mashwani ZUR. Understanding the potential of bio-fabricated non-oxidative silver nanoparticles to eradicateLeishmaniaand plant bacterial pathogens. Applied Nanoscience. 2020;10:2057-2067
  27. 27. Ismail HH, Hasoon SA, Saheb EJ. The anti-leishmaniasis activity of green synthesis silver oxide nanoparticles. Annals of Tropical Medicine and Public Health. 2019;22:28-38
  28. 28. Alti D, Veeramohan Rao M, Rao DN, Maurya R, Kalangi SK. Gold-silver bimetallic nanoparticles reduced with herbal leaf extracts induce ROS-mediated death in both promastigote and amastigote stages ofLeishmania donovani. ACS Omega. 2020;5:16238-16245
  29. 29. Prasanna P, Kumar P, Mandal S, Patyal T, Patyal T, Kumar S, et al. Synthesis of 7, 8-dihydroxyflavone functionalized gold nanoparticles and its mechanism of action againstLeishmania donovani. Research Square. 2020;16(21):1-29
  30. 30. Saleh AH. Potential role of titanium dioxide (TiO2) nanoparticles against the toxicity ofLeishmania tropicain adult albino male rats. Journal of Global Pharma Technology. 2019;11(3):453-457
  31. 31. Naz S, Islam M, Tabassum S, Fernandes NF, Carcache de Blanco EJ, Zia M. Green synthesis of hematite (α-Fe2O3) nanoparticles usingRhus punjabensisextract and their biomedical prospect in pathogenic diseases and cancer. Journal of Molecular Structure. 2019;1185:1-7
  32. 32. Khalil AT, Ovais M, Ullah I, Ali M, Jan SA, Shinwari ZK, et al. Bioinspired synthesis of pure massicot phase lead oxide nanoparticles and assessment of their biocompatibility, cytotoxicity andin-vitrobiological properties. Arabian Journal of Chemistry. 2020;13:916-931
  33. 33. Ain QU, Islam A, Nadhman A, Yasinzai M. Comparative analysis of chemically and biologically synthesized iron oxide nanoparticles againstLeishmania tropica. bioRxiv 2019
  34. 34. Abbasi BA, Iqbal J, Mahmood T, Ahmad R, Kanwal S, Afridi S. Plant-mediated synthesis of nickel oxide nanoparticles (NiO) viaGeranium wallichianum: Characterization and different biological applications. Materials Research Express. 2019;6:0850a7
  35. 35. Momeni A, Rasoolian M, Momeni A, Navaei A, Emami S, Shaker Z, et al. Development of liposomes loaded with anti-leishmanial drugs for the treatment of cutaneous leishmaniasis. Journal of Liposome Research. 2013;23:134-144
  36. 36. Kaye P, Scott P. Leishmaniasis: Complexity at the host-pathogen interface. Nature Reviews. Microbiology. 2011;9:604-615
  37. 37. Aditya NP, Chimote G, Gunalan K, Banerjee R, Patankar S, Madhusudhan B. Curcuminoids-loaded liposomes in combination with arteether protects againstPlasmodium bergheiinfection in mice. Experimental Parasitology. 2012;131:292-299
  38. 38. Barros NB, Migliaccio V, Facundo VA, Ciancaglini P, Stábeli RG, Nicolete R, et al. Liposomal-lupane system as alternative chemotherapy against cutaneous leishmaniasis: Macrophage as target cell. Experimental Parasitology. 2013;135:337-343
  39. 39. Duarte MC, Lagedos LMRR, Lage DP, Martins VT, Carvalho AMRS, Roatt BM, et al. Treatment of murine visceral leishmaniasis using an 8-hydroxyquinoline-containing polymeric micelle system. Parasitology International. 2016;65:728-736
  40. 40. Calvo A, Moreno E, Larrea E, Sanmartin C, Irache JM, Espuelas S. Berberine-loaded liposomes for the treatment ofLeishmania infantum-infected Balb/c mice. Pharmaceutics. 2020;12:858
  41. 41. Saljoughian N, Zahedifard F, Doroud D, Doustdari F, Vasei M, Papadopoulou B, et al. Cationic solid-lipid nanoparticles are as efficient as electroporation in DNA vaccination against visceral leishmaniasis in mice. Parasite Immunology. 2013;35:397-408
  42. 42. Noormehr H, Zavaran Hosseini A, Soudi S, Beyzay F. Enhancement of Th1 immune response againstLeishmaniacysteine peptidase A, B by PLGA nanoparticle. International Immunopharmacology. 2018;59:97-105
  43. 43. Olekhnovitch R, Ryffel B, Müller AJ, Bousso P. Collective nitric oxide production provides tissue-wide immunity duringLeishmaniainfection. The Journal of Clinical Investigation. 2014;124:1711-1722
  44. 44. Rosas-Hernandez H, Jimenez-Badillo S, Martinez-Cuevas PP, Gracia-Espino E, Terrones H, Terrones M, et al. Effects of 45-nm silver nanoparticles on coronary endothelial cells and isolated rat aortic rings. Toxicology Letters. 2009;191:305-313
  45. 45. Fanti JR, Tomiotto-Pellissier F, Miranda-Sapla MM, Cataneo AHD, Andrade CGTJ, Panis C, et al. Biogenic silver nanoparticles inducingLeishmania amazonensispromastigote and amastigote deathin vitro. Acta Tropica. 2018;178:46-54
  46. 46. Shoaib Sarwar H, Varikuti S, Farhan Sohail M, Sarwar M, Akhtar S, Satoskar AR, et al. Oral delivery and enhanced efficacy of antimonal drug through macrophage-guided multifunctional nanocargoes against visceral leishmaniasis. European Journal of Pharmaceutics and Biopharmaceutics. 2020;152:307-317
  47. 47. Park E-J, Yi J, Kim Y, Choi K, Park K. Silver nanoparticles induce cytotoxicity by a Trojan-horse type mechanism. Toxicology In Vitro. 2010;24:872-878
  48. 48. Kruszewski M, Brzoska K, Brunborg G, Asare N, Dobrzynska M, Dušinská M, et al. Toxicity of silver nanomaterials in higher eukaryotes. Advances in Molecular Toxicology. 2011;5:179-218
  49. 49. Zahir AA, Chauhan IS, Bagavan A, Kamaraj C, Elango G, Shankar J, et al. Green synthesis of silver and titanium dioxide nanoparticles usingEuphorbia prostrataextract shows shift from apoptosis to G0/G1Arrest followed by necrotic cell death inLeishmania donovani. Antimicrobial Agents and Chemotherapy. 2015;59:4782-4799
  50. 50. AshaRani PV, Low Kah Mun G, Hande MP, Valiyaveettil S. Cytotoxicity and genotoxicity of silver nanoparticles in human cells. ACS Nano. 2009;3:279-290

Written By

Nargis Shaheen, Chaitenya Verma and Naveeda Akhter Qureshi

Submitted: August 1st, 2021 Reviewed: December 9th, 2021 Published: April 13th, 2022