Generic placeholder image

Current Drug Metabolism

Editor-in-Chief

ISSN (Print): 1389-2002
ISSN (Online): 1875-5453

Review Article

Anti-leishmanial Nanotherapeutics: A Current Perspective

Author(s): Aditi Shah and Souvik Sen Gupta*

Volume 20, Issue 6, 2019

Page: [473 - 482] Pages: 10

DOI: 10.2174/1389200219666181022163424

Price: $65

Abstract

Background: Leishmaniasis is a dreaded disease caused by protozoan parasites belonging to the genus Leishmania which results in significant morbidity and mortality worldwide. There are no vaccines available currently for the treatment of Leishmaniasis and chemotherapy still remains the mainstay for anti-leishmanial therapeutics. However, toxicity, reduced bioavailability, high cost and chemoresistance are the principal problems which limit the use of the available drugs. In this context, anti-leishmanial nanotherapeutics may show the way for effective treatment of this dreaded disease.

Methods: We carried out extensive literature search of bibliographic database using keywords strictly within the scope of the present study for peer reviewed research articles. We focused specifically on articles related to the application of nanotechnology in drug development, drug delivery and vaccine delivery for anti-leishmanial therapeutics.

Results: This study shows the immense potential of the application of nanotechnology in the field of anti-leishmanial therapeutics. This will aid the targeted delivery of different drugs which is expected to increase the bioavailability, reduce toxicity and also address the problem of chemoresistance.

Conclusion: We surmise that exciting research in the field of anti-leishmanial nanotherapeutics is already showing the promise for effective applicability. Though direct use of nanoparticles as therapeutic agents does not seem to be a good option, the application of nanotechnology in this field for vaccine development is still in its early days. The nano based drug delivery system for anti-leishmanial therapeutics has evolved considerably over the past ten years and holds the potential to drastically change the landscape of anti-leishmanial therapeutics.

Keywords: Leishmania, Leishmaniasis, anti-leishmanial therapeutics, nanoparticles, nanotherapeutics, drug delivery, vaccine.

Graphical Abstract

[1]
World Health Organization, Leishmaniasis, 2018 http://www.who.int/en/news-room/fact-sheets/detail/leishmaniasis (Accessed May 16, 2018).
[2]
Drugs for Neglected Diseases initiative, About Leishmaniasis, 2018, https://www.dndi.org/diseases-projects/leishmaniasis/ (Accessed May 16, 2018).
[3]
Desjeux, P. Leishmaniasis: Current situation and new perspectives. Comp. Immunol. Microbiol. Infect. Dis., 2004, 27, 305-318.
[4]
Bhargava, P.; Singh, R. Developments in diagnosis and antileishmanial drugs. Interdiscip. Perspect. Infect. Dis., 2012, 2012626838
[5]
Cupolillo, E.; Brahim, L.R.; Toaldo, C.B.; De Oliveira-Neto, M.P.; De Brito, M.E.; Falqueto, A.; De Farias Naiff, M.; Grimaldi, G., Jr Genetic polymorphism and molecular epidemiology of Leishmania (Viannia) braziliensis from different hosts and geographic areas in Brazil. J. Clin. Microbiol., 2003, 41, 3126-3132.
[6]
Centres for Disease Control and Prevention, U.S. Department of Health and Human Services, Parasites-Leishmaniasis, 2018; https://www.cdc.gov/parasites/leishmaniasis/index.html (Accessed May 16, 2018).
[7]
Handman, E. Leishmaniasis: Current status of vaccine development. Clin. Microbiol. Rev., 2001, 14, 229-243.
[8]
Peters, W.; Evans, D.A.; Lanham, S.M. Importance of parasite identification in cases of leishmaniasis. J. R. Soc. Med., 1983, 76, 540-542.
[9]
Prasad, L.S. Kala azar. Indian J. Pediatr., 1999, 66, 539-546.
[10]
Danesh-Bahreini, M.A.; Shokri, J.; Samiei, A.; Kamali-Sarvestani, E.; Barzegar-Jalali, M.; Mohammadi-Samani, S. Nanovaccine for leishmaniasis: Preparation of chitosan nanoparticles containing Leishmania superoxide dismutase and evaluation of its immunogenicity in BALB/c mice. Int. J. Nanomedicine, 2011, 6, 835-842.
[11]
Gutierrez, V.; Seabra, A.B.; Reguera, R.M.; Khandare, J.; Calderon, M. New approaches from nanomedicine for treating leishmaniasis. Chem. Soc. Rev., 2016, 45, 152-168.
[12]
Rees, P.H.; Kager, P.A.; Wellde, B.T.; Hockmeyer, W.T. The response of Kenyan kala-azar to treatment with sodium stibogluconate. Am. J. Trop. Med. Hyg., 1984, 33, 357-361.
[13]
Salotra, P.; Singh, R. Challenges in the diagnosis of post kala-azar dermal leishmaniasis. Indian J. Med. Res., 2006, 123, 295-310.
[14]
Reyburn, H.; Rowland, M.; Mohsen, M.; Khan, B.; Davies, C. The prolonged epidemic of anthroponotic cutaneous leishmaniasis in Kabul, Afghanistan: ‘Bringing down the neighbourhood’. Trans. R. Soc. Trop. Med. Hyg., 2003, 97, 170-176.
[15]
Goto, H.; Lindoso, J.A. Current diagnosis and treatment of cutaneous and mucocutaneous leishmaniasis. Expert Rev. Anti Infect. Ther., 2010, 8, 419-433.
[16]
Reithinger, R.; Dujardin, J.C.; Louzir, H.; Pirmez, C.; Alexander, B.; Brooker, S. Cutaneous leishmaniasis. Lancet Infect. Dis., 2007, 7, 581-596.
[17]
Haldar, A.K.; Sen, P.; Roy, S. Use of antimony in the treatment of leishmaniasis: Current status and future directions. Mol. Biol. Int., 2011, 2011571242
[18]
Tiwari, N.; Gedda, M.R.; Tiwari, V.K.; Singh, S.P.; Singh, R.K. Limitations of current therapeutic options, possible drug targets and scope of natural products in control of leishmaniasis. Mini Rev. Med. Chem., 2018, 18, 26-41.
[19]
Singh, O.P.; Singh, B.; Chakravarty, J.; Sundar, S. Current challenges in treatment options for visceral leishmaniasis in India: A public health perspective. Infect. Dis. Poverty, 2016, 5, 19.
[20]
Mukherjee, A.; Padmanabhan, P.K.; Sahani, M.H.; Barrett, M.P.; Madhubala, R. Roles for mitochondria in pentamidine susceptibility and resistance in Leishmania donovani. Mol. Biochem. Parasitol., 2006, 145, 1-10.
[21]
Sundar, S.; Singh, A. Recent developments and future prospects in the treatment of visceral leishmaniasis. Ther. Adv. Infect. Dis., 2016, 3, 98-109.
[22]
Freitas-Junior, L.H.; Chatelain, E.; Kim, H.A.; Siqueira-Neto, J.L. Visceral leishmaniasis treatment: What do we have, what do we need and how to deliver it? Int. J. Parasitol. Drugs Drug Resist., 2012, 2, 11-19.
[23]
Sundar, S.; Singh, A.; Chakravarty, J.; Rai, M. Efficacy and safety of miltefosine in treatment of post-kala-azar dermal leishmaniasis. ScientificWorldJournal, 2015, 2015414378
[24]
Dorlo, T.P.; Balasegaram, M.; Beijnen, J.H.; de Vries, P.J. Miltefosine: A review of its pharmacology and therapeutic efficacy in the treatment of leishmaniasis. J. Antimicrob. Chemother., 2012, 67, 2576-2597.
[25]
Marinho, F.A.; Goncalves, K.C.; Oliveira, S.S.; Oliveira, A.C.; Bellio, M.; d’Avila-Levy, C.M.; Santos, A.L.; Branquinha, M.H. Miltefosine induces programmed cell death in leishmania amazonensis promastigotes. Mem. Inst. Oswaldo Cruz, 2011, 106, 507-519.
[26]
Mishra, J.; Singh, S. Miltefosine resistance in Leishmania donovani involves suppression of oxidative stress-induced programmed cell death. Exp. Parasitol., 2013, 135, 397-406.
[27]
Chawla, B.; Jhingran, A.; Panigrahi, A.; Stuart, K.D.; Madhubala, R. Paromomycin affects translation and vesicle-mediated trafficking as revealed by proteomics of paromomycin -susceptible -resistant Leishmania donovani. PLoS One, 2011, 6e26660
[28]
Hendrickx, S.; Mondelaers, A.; Eberhardt, E.; Delputte, P.; Cos, P.; Maes, L. In vivo selection of paromomycin and miltefosine resistance in Leishmania donovani and L. infantum in a Syrian hamster model. Antimicrob. Agents Chemother., 2015, 59, 4714-4718.
[29]
Singh, R.; Lillard, J.W., Jr Nanoparticle-based targeted drug delivery. Exp. Mol. Pathol., 2009, 86, 215-223.
[30]
Morachis, J.M.; Mahmoud, E.A.; Almutairi, A. Physical and chemical strategies for therapeutic delivery by using polymeric nanoparticles. Pharmacol. Rev., 2012, 64, 505-519.
[31]
Alavi, M.; Karimi, N.; Safaei, M. Application of various types of liposomes in drug delivery systems. Adv. Pharm. Bull., 2017, 7, 3-9.
[32]
Hua, S.; De Matos, M.B.C.; Metselaar, J.M.; Storm, G. Current trends and challenges in the clinical translation of nanoparticulate nanomedicines: Pathways for translational development and commercialization. Front. Pharmacol., 2018, 9, 790.
[33]
Gowda, R.; Kardos, G.; Sharma, A.; Singh, S.; Robertson, G.P. Nanoparticle-based celecoxib and plumbagin for the synergistic treatment of melanoma. Mol. Cancer Ther., 2017, 16, 440-452.
[34]
Jebali, A.; Kazemi, B. Nano-based antileishmanial agents: A toxicological study on nanoparticles for future treatment of cutaneous leishmaniasis. Toxicol. In Vitro, 2013, 27, 1896-1904.
[35]
Sabella, S.; Carney, R.P.; Brunetti, V.; Malvindi, M.A.; Al-Juffali, N.; Vecchio, G.; Janes, S.M.; Bakr, O.M.; Cingolani, R.; Stellacci, F.; Pompa, P.P. A general mechanism for intracellular toxicity of metal-containing nanoparticles. Nanoscale, 2014, 6, 7052-7061.
[36]
Singh, S.; Sharma, A.; Robertson, G.P. Realizing the clinical potential of cancer nanotechnology by minimizing toxicologic and targeted delivery concerns. Cancer Res., 2012, 72, 5663-5668.
[37]
Jain, K.; Jain, N.K. Novel therapeutic strategies for treatment of visceral leishmaniasis. Drug Discov. Today, 2013, 18, 1272-1281.
[38]
Veerareddy, P.R.; Vobalaboina, V.; Ali, N. Antileishmanial activity, pharmacokinetics and tissue distribution studies of mannose-grafted amphotericin B lipid nanospheres. J. Drug Target., 2009, 17, 140-147.
[39]
Italia, J.L.; Yahya, M.M.; Singh, D.; Ravi Kumar, M.N. Biodegradable nanoparticles improve oral bioavailability of amphotericin B and show reduced nephrotoxicity compared to intravenous Fungizone. Pharm. Res., 2009, 26, 1324-1331.
[40]
Nahar, M.; Jain, N.K. Preparation, characterization and evaluation of targeting potential of amphotericin B-loaded engineered PLGA nanoparticles. Pharm. Res., 2009, 26, 2588-2598.
[41]
Singodia, D.; Khare, P.; Dube, A.; Talegaonkar, S.; Khar, R.K.; Mishra, P.R. Development and performance evaluation of alginate-capped amphotericin B lipid nanoconstructs against visceral leishmaniasis. J. Biomed. Nanotechnol., 2011, 7, 123-124.
[42]
Italia, J.L.; Kumar, M.N.; Carter, K.C. Evaluating the potential of polyester nanoparticles for per oral delivery of amphotericin B in treating visceral leishmaniasis. J. Biomed. Nanotechnol., 2012, 8, 695-702.
[43]
Kansal, S.; Tandon, R.; Dwivedi, P.; Misra, P.; Verma, P.R.; Dube, A.; Mishra, P.R. Development of nanocapsules bearing doxorubicin for macrophage targeting through the phosphatidylserine ligand: A system for intervention in visceral leishmaniasis. J. Antimicrob. Chemother., 2012, 67, 2650-2660.
[44]
Asthana, S.; Jaiswal, A.K.; Gupta, P.K.; Pawar, V.K.; Dube, A.; Chourasia, M.K. Immunoadjuvant chemotherapy of visceral leishmaniasis in hamsters using amphotericin B-encapsulated nanoemulsion template-based chitosan nanocapsules. Antimicrob. Agents Chemother., 2013, 57, 1714-1722.
[45]
De Carvalho, R.F.; Ribeiro, I.F.; Miranda-Vilela, A.L.; De Souza Filho, J.; Martins, O.P.; Cintra e Silva Dde, O.; Tedesco, A.C.; Lacava, Z.G.; Bao, S.N.; Sampaio, R.N. Leishmanicidal activity of amphotericin B encapsulated in PLGA-DMSA nanoparticles to treat cutaneous leishmaniasis in C57BL/6 mice. Exp. Parasitol., 2013, 135, 217-222.
[46]
Ribeiro, T.G.; Chavez-Fumagalli, M.A.; Valadares, D.G.; Franca, J.R.; Rodrigues, L.B.; Duarte, M.C.; Lage, P.S.; Andrade, P.H.; Lage, D.P.; Arruda, L.V.; Abanades, D.R.; Costa, L.E.; Martins, V.T.; Tavares, C.A.; Castilho, R.O.; Coelho, E.A.; Faraco, A.A. Novel targeting using nanoparticles: An approach to the development of an effective anti-leishmanial drug-delivery system. Int. J. Nanomedicine, 2014, 9, 877-890.
[47]
Jain, V.; Gupta, A.; Pawar, V.K.; Asthana, S.; Jaiswal, A.K.; Dube, A.; Chourasia, M.K. Chitosan-assisted immunotherapy for intervention of experimental leishmaniasis via amphotericin B-loaded solid lipid nanoparticles. Appl. Biochem. Biotechnol., 2014, 174, 1309-1330.
[48]
Gupta, P.K.; Jaiswal, A.K.; Asthana, S.; Verma, A.; Kumar, V.; Shukla, P.; Dwivedi, P.; Dube, A.; Mishra, P.R. Self assembled ionically sodium alginate cross-linked amphotericin B encapsulated glycol chitosan stearate nanoparticles: Applicability in better chemotherapy and non-toxic delivery in visceral leishmaniasis. Pharm. Res., 2015, 32, 1727-1740.
[49]
Jain, K.; Verma, A.K.; Mishra, P.R.; Jain, N.K. Characterization and evaluation of amphotericin B loaded MDP conjugated poly(propylene imine) dendrimers. Nanomedicine, 2015, 11, 705-713.
[50]
Asthana, S.; Gupta, P.K.; Jaiswal, A.K.; Dube, A.; Chourasia, M.K. Overexpressed macrophage mannose receptor targeted nanocapsules- mediated cargo delivery approach for eradication of resident parasite: In vitro and in vivo studies. Pharm. Res., 2015, 32, 2663-2677.
[51]
Barros, D.; Costa Lima, S.A.; Cordeiro-da-Silva, A. Surface functionalization of polymeric nanospheres modulates macrophage activation: Relevance in leishmaniasis therapy. Nanomedicine (Lond.), 2015, 10, 387-403.
[52]
Asthana, S.; Gupta, P.K.; Jaiswal, A.K.; Dube, A.; Chourasia, M.K. Targeted chemotherapy of visceral leishmaniasis by lactoferrin-appended amphotericin B-loaded nanoreservoir: In vitro and in vivo studies. Nanomedicine (Lond.), 2015, 10, 1093-1109.
[53]
Want, M.Y.; Islamuddin, M.; Chouhan, G.; Ozbak, H.A.; Hemeg, H.A.; Dasgupta, A.K.; Chattopadhyay, A.P.; Afrin, F. Therapeutic efficacy of artemisinin-loaded nanoparticles in experimental visceral leishmaniasis. Colloids Surf. B Biointerfaces, 2015, 130, 215-221.
[54]
Kumar, R.; Sahoo, G.C.; Pandey, K.; Das, V.N.; Topno, R.K.; Ansari, M.Y.; Rana, S.; Das, P. Development of PLGA-PEG encapsulated miltefosine based drug delivery system against visceral leishmaniasis. Mater. Sci. Eng. C Mater. Biol. Appl., 2016, 59, 748-753.
[55]
Heidari-Kharaji, M.; Taheri, T.; Doroud, D.; Habibzadeh, S.; Rafati, S. Solid lipid nanoparticle loaded with paromomycin: in vivo efficacy against Leishmania tropica infection in BALB/c mice model. Appl. Microbiol. Biotechnol., 2016, 100, 7051-7060.
[56]
Heidari-Kharaji, M.; Taheri, T.; Doroud, D.; Habibzadeh, S.; Badirzadeh, A.; Rafati, S. Enhanced paromomycin efficacy by solid lipid nanoparticle formulation against Leishmania in mice model. Parasite Immunol., 2016, 38, 599-608.
[57]
Chaurasia, M.; Singh, P.K.; Jaiswal, A.K.; Kumar, A.; Pawar, V.K.; Dube, A.; Paliwal, S.K.; Chourasia, M.K. Bioinspired Calcium Phosphate Nanoparticles Featuring as Efficient Carrier and Prompter for Macrophage Intervention in Experimental Leishmaniasis. Pharm. Res., 2016, 33, 2617-2629.
[58]
Da Gama Bitencourt, J.J.; Pazin, W.M.; Ito, A.S.; Barioni, M.B.; De Paula Pinto, C.; Santos, M.A.; Guimaraes, T.H.; Santos, M.R.; Valduga, C.J. Miltefosine-loaded lipid nanoparticles: Improving miltefosine stability and reducing its hemolytic potential toward erythtocytes and its cytotoxic effect on macrophages. Biophys. Chem., 2016, 217, 20-31.
[59]
Ghosh, S.; Kar, N.; Bera, T. Oleanolic acid loaded poly lactic coglycolic acid- vitamin E TPGS nanoparticles for the treatment of Leishmania donovani infected Visceral leishmaniasis. Int. J. Biol. Macromol., 2016, 93(Pt A), 961-970.
[60]
Das, S.; Ghosh, S.; De, A.K.; Bera, T. Oral delivery of ursolic acid-loaded nanostructured lipid carrier coated with chitosan oligosaccharides: Development, characterization, in vitro and in vivo assessment for the therapy of leishmaniasis. Int. J. Biol. Macromol., 2017, 102, 996-1008.
[61]
Biswaro, L.S.; Garcia, M.P.; da Silva, J.R.; Neira Fuentes, L.F.; Vera, A.; Escobar, P.; Azevedo, R.B. Itraconazole encapsulated PLGA-nanoparticles covered with mannose as potential candidates against leishmaniasis. J. Biomed. Mater. Res. B Appl. Biomater., 2018. [epub ahead of print].
[62]
Mehrizi, T.Z.; Ardestani, M.S.; Khamesipour, A.; Hoseini, M.H.M.; Mosaffa, N.; Anissian, A.; Ramezani, A. Reduction toxicity of Amphotericin B through loading into a novel nanoformulation of anionic linear globular dendrimer for improve treatment of leishmania major. J. Mater. Sci. Mater. Med., 2018, 29, 125.
[63]
Prajapati, V.K.; Awasthi, K.; Gautam, S.; Yadav, T.P.; Rai, M.; Srivastava, O.N.; Sundar, S. Targeted killing of Leishmania donovani in vivo and in vitro with amphotericin B attached to functionalized carbon nanotubes. J. Antimicrob. Chemother., 2011, 66, 874-879.
[64]
Saudagar, P.; Dubey, V.K. Carbon nanotube based betulin formulation shows better efficacy against Leishmania parasite. Parasitol. Int., 2014, 63, 772-776.
[65]
Allahverdiyev, A.M.; Abamor, E.S.; Bagirova, M.; Ustundag, C.B.; Kaya, C.; Kaya, F.; Rafailovich, M. Antileishmanial effect of silver nanoparticles and their enhanced antiparasitic activity under ultraviolet light. Int. J. Nanomedicine, 2011, 6, 2705-2714.
[66]
Soflaei, S.; Dalimi, A.; Ghaffarifar, F.; Shakibaie, M.; Shahverdi, A.R.; Shafiepour, M. In vitro antiparasitic and apoptotic effects of antimony sulfide nanoparticles on leishmania infantum. J. Parasitol. Res., 2012, 2012756568
[67]
Nadhman, A.; Nazir, S.; Khan, M.I.; Arooj, S.; Bakhtiar, M.; Shahnaz, G.; Yasinzai, M. PEGylated silver doped zinc oxide nanoparticles as novel photosensitizers for photodynamic therapy against Leishmania. Free Radic. Biol. Med., 2014, 77, 230-238.
[68]
Ahmad, A.; Wei, Y.; Syed, F.; Khan, S.; Khan, G.M.; Tahir, K.; Khan, A.U.; Raza, M.; Khan, F.U.; Yuan, Q. Isatis tinctoria mediated synthesis of amphotericin B-bound silver nanoparticles with enhanced photoinduced antileishmanial activity: A novel green approach. J. Photochem. Photobiol. B, 2016, 161, 17-24.
[69]
Tiwari, B.; Pahuja, R.; Kumar, P.; Rath, S.K.; Gupta, K.C.; Goyal, N. Nanotized curcumin and miltefosine, a potential combination for treatment of experimental visceral leishmaniasis. Antimicrob. Agents Chemother., 2017, 61 pii: e01169-e16.
[70]
Firouzmand, H.; Sahranavard, M.; Badiee, A.; Khamesipour, A.; Alavizadeh, S.H.; Samiei, A.; Soroush, D.; Tavassoti Kheiri, M.; Mahboudi, F.; Jaafari, M.R. The role of LPD-nanoparticles containing recombinant major surface glycoprotein of Leishmania (rgp63) in protection against leishmaniasis in murine model. Immunopharmacol. Immunotoxicol., 2018, 40, 72-82.
[71]
Santos, D.M.; Carneiro, M.W.; de Moura, T.R.; Fukutani, K.; Clarencio, J.; Soto, M.; Espuelas, S.; Brodskyn, C.; Barral, A.; Barral-Netto, M.; De Oliveira, C.I. Towards development of novel immunization strategies against leishmaniasis using PLGA nanoparticles loaded with kinetoplastid membrane protein-11. Int. J. Nanomedicine, 2012, 7, 2115-2127.
[72]
Margaroni, M.; Agallou, M.; Athanasiou, E.; Kammona, O.; Kiparissides, C.; Gaitanaki, C.; Karagouni, E. Vaccination with poly(D,L-lactide-co-glycolide) nanoparticles loaded with soluble Leishmania antigens and modified with a TNFalpha-mimicking peptide or monophosphoryl lipid A confers protection against experimental visceral leishmaniasis. Int. J. Nanomedicine, 2017, 12, 6169-6184.
[73]
Tabatabaie, F.; Samarghandi, N.; Zarrati, S.; Maleki, F.; Ardestani, M.S.; Elmi, T.; Mosawi, S.H. Induction of immune responses by DNA vaccines formulated with dendrimer and poly (Methyl Methacrylate) (PMMA) nano-adjuvants in BALB/c mice infected with leishmania major. Open Access Maced. J. Med. Sci., 2018, 6, 229-236.

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy