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Current Pharmaceutical Design


ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Review Article

Antimicrobial Peptides-based Nanostructured Delivery Systems: An Approach for Leishmaniasis Treatment

Author(s): Adrian Rodríguez-Carlos, Fidel Martinez-Gutierrez, Flor Torres-Juarez and Bruno Rivas-Santiago*

Volume 25 , Issue 14 , 2019

Page: [1593 - 1603] Pages: 11

DOI: 10.2174/1381612825666190628152842

Price: $65


Background: Leishmaniasis is a major health problem mainly in tropical and subtropical areas worldwide, although in the last decades it has been treated with the use of conventional drugs such as amphotericin, the emergence of multidrug-resistant strains has raised a warning signal to the public health systems thus a new call for the creation of new leishmanicidal drugs is needed.

Methods: The goal of this review was to explore the potential use of antimicrobial peptides-based nanostructured delivery systems as an approach for leishmaniasis treatment.

Results: Within these new potential drugs, human host defense peptides (HDP) can be included given their remarkable antimicrobial activity and their outstanding immunomodulatory functions for the therapy of leishmaniasis.

Conclusion: Though several approaches have been done using these peptides, new ways for delivering HDPs need to be analyzed, such is the case for nanotechnology.

Keywords: Leishmaniasis, nanotechnologies, nanoparticles, host defense peptides, antimicrobial peptides, therapy.

Torres-Guerrero E, Quintanilla-Cedillo MR, Ruiz-Esmenjaud J, Arenas R. Leishmaniasis: a review. F1000 Res 2017; 6: 750. []. [PMID: 28649370].
Reithinger R, Dujardin JC, Louzir H, Pirmez C, Alexander B, Brooker S. Cutaneous leishmaniasis. Lancet Infect Dis 2007; 7(9): 581-96. []. [PMID: 17714672].
Akhoundi M, Kuhls K, Cannet A, et al. A Historical Overview of the Classification, Evolution, and Dispersion of Leishmania Parasites and Sandflies. PLoS Negl Trop Dis 2016; 10(3)e0004349 []. [PMID: 26937644].
Ghorbani M, Farhoudi R. Leishmaniasis in humans: drug or vaccine therapy? Drug Des Devel Ther 2017; 12: 25-40. []. [PMID: 29317800].
Sunyoto T, Boelaert M, Meheus F. Understanding the economic impact of leishmaniasis on households in endemic countries: a systematic review. Expert Rev Anti Infect Ther 2019; 17(1): 57-69. []. [PMID: 30513027].
Organization WH. Leishmaniasis Factsheet. Bull World Health Organ 2017.
Savoia D. Recent updates and perspectives on leishmaniasis. J Infect Dev Ctries 2015; 9(6): 588-96. []. [PMID: 26142667].
Sundar S. Drug resistance in Indian visceral leishmaniasis. Trop Med Int Health 2001; 6(11): 849-54. []. [PMID: 11703838].
Mishra J, Saxena A, Singh S. Chemotherapy of leishmaniasis: Past, present and future. Curr Med Chem 2007; 14(10): 1153-69. []. [PMID: 17456028].
Martínez E, Torres-Guerrero E, Cortés E, Tejada D, Arenas R. Cryptococcus laurentii infection in a patient with cutaneous leishmaniasis. Int J Dermatol 2017; 56(3): e56-7. []. [PMID: 27666937].
Thakur CP. A single high dose treatment of kala-azar with Ambisome (amphotericin B lipid complex): A pilot study. Int J Antimicrob Agents 2001; 17(1): 67-70. []. [PMID: 11137652].
Organization WH. Organization WH. Report of a WHO informal Consultation on “Liposomal Amphotericin B in the Treatment of Visceral Leishmaniasis”. resources/AmBisome-Report.pdfIn: ed.^eds., 2005.
Sundar S, Chakravarty J. Liposomal amphotericin B and leishmaniasis: Dose and response. J Glob Infect Dis 2010; 2(2): 159-66. []. [PMID: 20606972].
Dorlo TP, Rijal S, Ostyn B, et al. Failure of miltefosine in visceral leishmaniasis is associated with low drug exposure. J Infect Dis 2014; 210(1): 146-53. []. [PMID: 24443541].
de Menezes JP, Guedes CE, Petersen AL, Fraga DB, Veras PS. Advances in Development of New Treatment for Leishmaniasis. BioMed Res Int 2015; 2015815023 []. [PMID: 26078965].
No JH. Visceral leishmaniasis: Revisiting current treatments and approaches for future discoveries. Acta Trop 2016; 155: 113-23. []. [PMID: 26748356].
Rajasekaran R, Chen YP. Potential therapeutic targets and the role of technology in developing novel antileishmanial drugs. Drug Discov Today 2015; 20(8): 958-68. []. [PMID: 25936844].
Hancock REW, Sahl H-G. Antimicrobial and host-defense peptides as new anti-infective therapeutic strategies. Nat Biotechnol 2006; 24(12): 1551-7. []. [PMID: 17160061].
Peters BM, Shirtliff ME, Jabra-Rizk MA. Antimicrobial peptides: primeval molecules or future drugs? PLoS Pathog 2010; 6(10)e1001067 []. [PMID: 21060861].
Zasloff M. Antimicrobial peptides of multicellular organisms. Nature 2002; 415(6870): 389-95. []. [PMID: 11807545].
Rivas-Santiago B, Sada E, Hernández-Pando R, Tsutsumi V. [Antimicrobial peptides in the innate immunity of infectious diseases]. [PMID: 16555536]. Salud Publica Mex 2006; 48(1): 62-71.
Zhang LJ, Gallo RL. Antimicrobial peptides. Curr Biol 2016; 26(1): R14-9. []. [PMID: 26766224].
Territo MC, Ganz T, Selsted ME, Lehrer R. Monocyte-chemotactic activity of defensins from human neutrophils. J Clin Invest 1989; 84(6): 2017-20. []. [PMID: 2592571].
Yang D, Chen Q, Chertov O, Oppenheim JJ. Human neutrophil defensins selectively chemoattract naive T and immature dendritic cells. J Leukoc Biol 2000; 68(1): 9-14. [PMID: 10914484].
Lehrer RI, Lu W. α-Defensins in human innate immunity. Immunol Rev 2012; 245(1): 84-112. []. [PMID: 22168415].
Dürr UHN, Sudheendra US, Ramamoorthy A. LL-37, the only human member of the cathelicidin family of antimicrobial peptides. Biochim Biophys Acta 2006; 1758(9): 1408-25. []. [PMID: 16716248].
De Yang Chen Q. Schmidt AP, et al LL-37, the neutrophil granule- and epithelial cell-derived cathelicidin, utilizes formyl peptide receptor-like 1 (FPRL1) as a receptor to chemoattract human peripheral blood neutrophils, monocytes, and T cells. J Exp Med 2000; 192(7): 1069-74. []. [PMID: 11015447].
Elssner A, Duncan M, Gavrilin M, Wewers MD. A novel P2X7 receptor activator, the human cathelicidin-derived peptide LL37, induces IL-1 beta processing and release. J Immunol 2004; 172(8): 4987-94. []. [PMID: 15067080].
Montreekachon P, Chotjumlong P, Bolscher JG, Nazmi K, Reutrakul V, Krisanaprakornkit S. Involvement of P2X(7) purinergic receptor and MEK1/2 in interleukin-8 up-regulation by LL-37 in human gingival fibroblasts. J Periodontal Res 2011; 46(3): 327-37. []. [PMID: 21338358].
Tokumaru S, Sayama K, Shirakata Y, et al. Induction of keratinocyte migration via transactivation of the epidermal growth factor receptor by the antimicrobial peptide LL-37. J Immunol 2005; 175(7): 4662-8. []. [PMID: 16177113].
Xhindoli D, Pacor S, Benincasa M, Scocchi M, Gennaro R, Tossi A. The human cathelicidin LL-37--A pore-forming antibacterial peptide and host-cell modulator. Biochim Biophys Acta 2016; 1858(3): 546-66. []. [PMID: 26556394].
Dabirian S, Taslimi Y, Zahedifard F, et al. Human neutrophil peptide-1 (HNP-1): a new anti-leishmanial drug candidate. PLoS Negl Trop Dis 2013; 7(10)e2491 []. [PMID: 24147170].
Abdossamadi Z, Seyed N, Zahedifard F, et al. Human Neutrophil Peptide 1 as immunotherapeutic agent against Leishmania infected BALB/c mice. PLoS Negl Trop Dis 2017; 11(12)e0006123 []. [PMID: 29253854].
Dos Santos JC, Heinhuis B, Gomes RS, et al. Cytokines and microbicidal molecules regulated by IL-32 in THP-1-derived human macrophages infected with New World Leishmania species. PLoS Negl Trop Dis 2017; 11(2)e0005413 []. [PMID: 28241012].
Kulkarni MM, McMaster WR, Kamysz E, Kamysz W, Engman DM, McGwire BS. The major surface-metalloprotease of the parasitic protozoan, Leishmania, protects against antimicrobial peptide-induced apoptotic killing. Mol Microbiol 2006; 62(5): 1484-97. []. [PMID: 17074074].
Kulkarni MM, Barbi J, McMaster WR, Gallo RL, Satoskar AR, McGwire BS. Mammalian antimicrobial peptide influences control of cutaneous Leishmania infection. Cell Microbiol 2011; 13(6): 913-23. []. [PMID: 21501359].
de la Fuente-Núñez C, Silva ON, Lu TK, Franco OL. Antimicrobial peptides: Role in human disease and potential as immunotherapies. Pharmacol Ther 2017; 178: 132-40. []. [PMID: 28435091].
Rivas-Santiago B, Serrano CJ, Enciso-Moreno JA. Susceptibility to infectious diseases based on antimicrobial peptide production. Infect Immun 2009; 77(11): 4690-5. []. [PMID: 19703980].
Arranz-Trullén J, Lu L, Pulido D, Bhakta S, Boix E. Host Antimicrobial Peptides: The Promise of New Treatment Strategies against Tuberculosis. Front Immunol 2017; 8: 1499. []. [PMID: 29163551].
Fehlbaum P, Rao M, Zasloff M, Anderson GM. An essential amino acid induces epithelial beta-defensin expression. Proc Natl Acad Sci USA 2000; 97(23): 12723-8. []. [PMID: 11058160].
Rivas-Santiago CE, Hernández-Pando R, Rivas-Santiago B. Immunotherapy for pulmonary TB: Antimicrobial peptides and their inducers. Immunotherapy 2013; 5(10): 1117-26. []. [PMID: 24088080].
Rivas-Santiago B, Castañeda-Delgado JE, Rivas Santiago CE, et al. Ability of innate defence regulator peptides IDR-1002, IDR-HH2 and IDR-1018 to protect against Mycobacterium tuberculosis infections in animal models. PLoS One 2013; 8(3)e59119 []. [PMID: 23555622].
Rivas-Santiago CE, Rivas-Santiago B, León DA, Castañeda-Delgado J, Hernández Pando R. Induction of β-defensins by l-isoleucine as novel immunotherapy in experimental murine tuberculosis. Clin Exp Immunol 2011; 164(1): 80-9. []. [PMID: 21235540].
Gonzalez-Curiel I, Trujillo V, Montoya-Rosales A, et al. 1,25-dihydroxyvitamin D3 induces LL-37 and HBD-2 production in keratinocytes from diabetic foot ulcers promoting wound healing: an in vitro model. PLoS One 2014; 9(10)e111355 []. [PMID: 25337708].
Nnoaham KE, Clarke A. Low serum vitamin D levels and tuberculosis: A systematic review and meta-analysis. Int J Epidemiol 2008; 37(1): 113-9. []. [PMID: 18245055].
Yamshchikov AV, Kurbatova EV, Kumari M, et al. Vitamin D status and antimicrobial peptide cathelicidin (LL-37) concentrations in patients with active pulmonary tuberculosis. Am J Clin Nutr 2010; 92(3): 603-11. []. [PMID: 20610636].
Liu PT, Stenger S, Li H, et al. Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response. Science 2006; 311(5768): 1770-3. []. [PMID: 16497887].
Denis M. Killing of Mycobacterium tuberculosis within human monocytes: Activation by cytokines and calcitriol. Clin Exp Immunol 1991; 84(2): 200-6. []. [PMID: 1902761].
Larcombe L, Orr P, Turner-Brannen E, Slivinski CR, Nickerson PW, Mookherjee N. Effect of vitamin D supplementation on Mycobacterium tuberculosis-induced innate immune responses in a Canadian Dené First Nations cohort. PLoS One 2012; 7(7)e40692 []. [PMID: 22866178].
Mily A, Rekha RS, Kamal SM, et al. Oral intake of phenylbutyrate with or without vitamin D3 upregulates the cathelicidin LL-37 in human macrophages: a dose finding study for treatment of tuberculosis. BMC Pulm Med 2013; 13: 23. []. [PMID: 23590701].
Raqib R, Sarker P, Bergman P, et al. Improved outcome in shigellosis associated with butyrate induction of an endogenous peptide antibiotic. Proc Natl Acad Sci USA 2006; 103(24): 9178-83. []. [PMID: 16740661].
Sarker P, Ahmed S, Tiash S, et al. Phenylbutyrate counteracts Shigella mediated downregulation of cathelicidin in rabbit lung and intestinal epithelia: a potential therapeutic strategy. PLoS One 2011; 6(6)e20637 []. [PMID: 21673991].
Raqib R, Sarker P, Mily A, et al. Efficacy of sodium butyrate adjunct therapy in shigellosis: A randomized, double-blind, placebo-controlled clinical trial. BMC Infect Dis 2012; 12: 111. []. [PMID: 22574737].
Steinmann J, Halldórsson S, Agerberth B, Gudmundsson GH. Phenylbutyrate induces antimicrobial peptide expression. Antimicrob Agents Chemother 2009; 53(12): 5127-33. []. [PMID: 19770273].
Kindrachuk J, Jenssen H, Elliott M, et al. A novel vaccine adjuvant comprised of a synthetic innate defence regulator peptide and CpG oligonucleotide links innate and adaptive immunity. Vaccine 2009; 27(34): 4662-71. []. [PMID: 19539585].
Cao D, Li H, Jiang Z, et al. Synthetic innate defence regulator peptide enhances in vivo immunostimulatory effects of CpG-ODN in newborn piglets. Vaccine 2010; 28(37): 6006-13. []. [PMID: 20637306].
Yang J, Mao M, Zhang S, et al. Innate defense regulator peptide synergizes with CpG ODN for enhanced innate intestinal immune responses in neonate piglets. Int Immunopharmacol 2012; 12(2): 415-24. []. [PMID: 22226751].
Hancock RE, Nijnik A, Philpott DJ. Modulating immunity as a therapy for bacterial infections. Nat Rev Microbiol 2012; 10(4): 243-54. []. [PMID: 22421877].
Rivas-Santiago B, Rivas Santiago CE, Castañeda-Delgado JE, León-Contreras JC, Hancock RE, Hernandez-Pando R. Activity of LL-37, CRAMP and antimicrobial peptide-derived compounds E2, E6 and CP26 against Mycobacterium tuberculosis. Int J Antimicrob Agents 2013; 41(2): 143-8. []. [PMID: 23141114].
Salay LC, Nobre TM, Colhone MC, et al. Dermaseptin 01 as antimicrobial peptide with rich biotechnological potential: study of peptide interaction with membranes containing Leishmania amazonensis lipid-rich extract and membrane models. J Pept Sci 2011; 17(10): 700-7. []. [PMID: 21805539].
Savoia D, Guerrini R, Marzola E, Salvadori S. Synthesis and antimicrobial activity of dermaseptin S1 analogues. Bioorg Med Chem 2008; 16(17): 8205-9. []. [PMID: 18676150].
Zampa MF, Araújo IM, Costa V, et al. Leishmanicidal activity and immobilization of dermaseptin 01 antimicrobial peptides in ultrathin films for nanomedicine applications. Nanomedicine (Lond) 2009; 5(3): 352-8. []. [PMID: 19215729].
Hernandez C, Mor A, Dagger F, et al. Functional and structural damage in Leishmania mexicana exposed to the cationic peptide dermaseptin. Eur J Cell Biol 1992; 59(2): 414-24. [PMID: 1493807].
Mangoni ML, Saugar JM, Dellisanti M, Barra D, Simmaco M, Rivas L. Temporins, small antimicrobial peptides with leishmanicidal activity. J Biol Chem 2005; 280(2): 984-90. []. [PMID: 15513914].
Akuffo H, Hultmark D, Engstöm A, Frohlich D, Kimbrell D. Drosophila antibacterial protein, cecropin A, differentially affects non-bacterial organisms such as Leishmania in a manner different from other amphipathic peptides. Int J Mol Med 1998; 1(1): 77-82. []. [PMID: 9852202].
Lynn MA, Kindrachuk J, Marr AK, et al. Effect of BMAP-28 antimicrobial peptides on Leishmania major promastigote and amastigote growth: Role of leishmanolysin in parasite survival. PLoS Negl Trop Dis 2011; 5(5)e1141 []. [PMID: 21655347].
do Nascimento VV, Mello Éde O, Carvalho LP, et al. PvD1 defensin, a plant antimicrobial peptide with inhibitory activity against Leishmania amazonensis. Biosci Rep 2015; 35(5)e00248 []. [PMID: 26285803].
Luque-Ortega JR, van’t Hof W, Veerman EC, Saugar JM, Rivas L. Human antimicrobial peptide histatin 5 is a cell-penetrating peptide targeting mitochondrial ATP synthesis in Leishmania. FASEB J 2008; 22(6): 1817-28. []. [PMID: 18230684].
Abdossamadi Z, Taheri T, Seyed N, et al. Live Leishmania tarentolae secreting HNP1 as an immunotherapeutic tool against Leishmania infection in BALB/c mice. Immunotherapy 2017; 9(13): 1089-102. []. [PMID: 29032739].
Campos-Salinas J, Caro M, Cavazzuti A, et al. Protective role of the neuropeptide Urocortin II against experimental sepsis and leishmaniasis by direct killing of pathogens. J Immunol 2013; 191: 6040-51. [].
Campos-Salinas J, Cavazzuti A, O’Valle F, et al. Therapeutic efficacy of stable analogues of vasoactive intestinal peptide against pathogens. J Biol Chem 2014; 289(21): 14583-99. []. [PMID: 24706753].
Marr AK, Cen S, Hancock REW, McMaster WR. Identification of Synthetic and Natural Host Defense Peptides with Leishmanicidal Activity. Antimicrob Agents Chemother 2016; 60(4): 2484-91. []. [PMID: 26883699].
Erfe MCB, David CV, Huang C, et al. Efficacy of synthetic peptides RP-1 and AA-RP-1 against Leishmania species in vitro and in vivo. Antimicrob Agents Chemother 2012; 56(2): 658-65. []. [PMID: 22123683].
Fang RH, Zhang L. Nanoparticle-Based Modulation of the Immune System. Annu Rev Chem Biomol Eng 2016; 7: 305-26. []. [PMID: 27146556].
Fang RH, Kroll AV, Zhang L. Nanoparticle-Based Manipulation of Antigen-Presenting Cells for Cancer Immunotherapy. Small 2015; 11(41): 5483-96. []. [PMID: 26331993].
Youan BB. Impact of nanoscience and nanotechnology on controlled drug delivery. Nanomedicine 2008; 3(4): 401-6. []. [PMID: 18694301].
Prasad M, Lambe UP, Brar B, et al. Nanotherapeutics: An insight into healthcare and multi-dimensional applications in medical sector of the modern world. Biomed Pharmacother 2018; 97: 1521-37. []. [PMID: 29793315].
Fang RH, Jiang Y, Fang JC, Zhang L. Cell membrane-derived nanomaterials for biomedical applications. Biomaterials 2017; 128: 69-83. []. [PMID: 28292726].
Fang RH, Hu CM, Zhang L. Nanoparticles disguised as red blood cells to evade the immune system. Expert Opin Biol Ther 2012; 12(4): 385-9. []. [PMID: 22332936].
Zhang S, Gao H, Bao G. Physical Principles of Nanoparticle Cellular Endocytosis. ACS Nano 2015; 9(9): 8655-71. []. [PMID: 26256227].
Baek S, Singh RK, Khanal D, et al. Smart multifunctional drug delivery towards anticancer therapy harmonized in mesoporous nanoparticles. Nanoscale 2015; 7(34): 14191-216. []. [PMID: 26260245].
Mir M, Ahmed N, Rehman AU. Recent applications of PLGA based nanostructures in drug delivery. Colloids Surf B Biointerfaces 2017; 159: 217-31. []. [PMID: 28797972].
Peres C, Matos AI, Conniot J, et al. Poly(lactic acid)-based particulate systems are promising tools for immune modulation. Acta Biomater 2017; 48: 41-57. []. [PMID: 27826003].
Nomura T, Routh AF. Benign preparation of aqueous core poly lactic-co-glycolic acid (PLGA) microcapsules. J Colloid Interface Sci 2018; 513: 1-9. []. [PMID: 29128617].
Athanasiou E, Agallou M, Tastsoglou S, et al. A Poly(Lactic-co-Glycolic) Acid Nanovaccine Based on Chimeric Peptides from Different Leishmania infantum Proteins Induces Dendritic Cells Maturation and Promotes Peptide-Specific IFNγ-Producing CD8+ T Cells Essential for the Protection against Experimental Visceral Leishmaniasis. Front Immunol 2017; 8: 684. []. [PMID: 28659922].
Hilchie AL, Wuerth K, Hancock RE. Immune modulation by multifaceted cationic host defense (antimicrobial) peptides. Nat Chem Biol 2013; 9(12): 761-8. []. [PMID: 24231617].
Kamhawi S, Oliveira F, Valenzuela JG. Using humans to make a human leishmaniasis vaccine. Sci Transl Med 2014; 6(234)234fs18 []. [PMID: 24786322].
Rivas-Santiago B, Rivas-Santiago C, Sada E, Hernández-Pando R. Prophylactic potential of defensins and L-isoleucine in tuberculosis household contacts: An experimental model. Immunotherapy 2015; 7(3): 207-13. []. [PMID: 25804474].
Xia X, Zhang L, Wang Y. The antimicrobial peptide cathelicidin-BF could be a potential therapeutic for Salmonella typhimurium infection. Microbiol Res 2015; 171: 45-51. []. [PMID: 25644952].
Abdossamadi Z, Seyed N, Zahedifard F, et al. Human Neutrophil Peptide 1 as immunotherapeutic agent against Leishmania infected BALB/c mice. PLoS Negl Trop Dis 2017; 11(12)e0006123 []. [PMID: 29253854].
Das S, Sardar AH, Abhishek K, Kumar A, Rabidas VN, Das P. Cathelicidin augments VDR-dependent anti-leishmanial immune response in Indian Post-Kala-Azar Dermal Leishmaniasis. Int Immunopharmacol 2017; 50: 130-8. []. [PMID: 28662432].
McGwire BS, Olson CL, Tack BF, Engman DM. Killing of African trypanosomes by antimicrobial peptides. J Infect Dis 2003; 188(1): 146-52. []. [PMID: 12825184].

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