Generic placeholder image

Current Reviews in Clinical and Experimental Pharmacology

Editor-in-Chief

ISSN (Print): 2772-4328
ISSN (Online): 2772-4336

Systematic Review Article

New Strategies in the Treatment of Diseases Caused by Acanthamoeba Based on Nanoparticles: A Systematic Review

Author(s): Pegah Shakib, Hamed Kalani, Muhammad Tahir Aleem, Roghiyeh Faridnia, Mustafa Zebardast Pour, Kobra Moradpour and Kourosh Cheraghipour*

Volume 19, Issue 1, 2024

Published on: 24 November, 2022

Page: [68 - 77] Pages: 10

DOI: 10.2174/2772432818666221111155119

Price: $65

Abstract

Background: Acanthamoeba is one of the opportunistic parasites with a global prevalence. Currently, due to the side effects and the emergence of drug resistance to this parasite, much research has been performed on the use of nano-drugs to treat Acanthamoeba-caused diseases. Therefore, this systematic review study aims to evaluate new strategies for treating diseases caused by Acanthamoeba based on nanoparticles (NPs).

Methods: We designed a systematic review based on the articles published in English between 2000 and 2022. Our search strategy was based on syntax and specific tags for each database, including ScienceDirect, PubMed, Scopus, Ovid, and Cochrane. From the articles, those that had inclusion criteria were selected, and their data were extracted and analyzed.

Results: In this study, 26 studies were selected. Metallic nanoparticles were mostly used against the Acanthamoeba species (80.7%). 19.2% of the studies used polymeric nanoparticles, and 3.8% used emulsion nanoparticles. Most studies (96.1%) were performed in vitro, and only one study (3.8%) was carried out in vivo. Silver NPs were the most used metallic nanoparticles in the studies. The best effect of the anti-Acanthamoeba compound was observed for green synthesized nanoparticles based on stabilization by plant gums, loaded with citrus fruits flavonoids hesperidin (HDN) and naringin (NRG) with a 100% growth inhibition at a concentration of 50 μg/mL.

Conclusion: This study showed that chlorhexidine and other plant metabolites loaded with silver and gold nanoparticles increase the anti-Acanthambae activity of these nanoparticles. However, green synthesized nanoparticles based on stabilization by plant gums, loaded with citrus fruits flavonoids hesperidin (HDN) and naringin (NRG), showed the best anti-Acanthambae effect. Nevertheless, further studies should be performed to determine their safety for human use.

Keywords: Acanthamoeba, nanoparticles, in vitro, in vivo, systematic review, parasites.

Graphical Abstract
[1]
Martinez AJ, Visvesvara GS. Free-living, amphizoic and opportunistic amebas. Brain Pathol 1997; 7(1): 583-98.
[http://dx.doi.org/10.1111/j.1750-3639.1997.tb01076.x] [PMID: 9034567]
[2]
La Scola B, Boyadjiev I, Greub G, Khamis A, Martin C, Raoult D. Amoeba-resisting bacteria and ventilator-associated pneumonia. Emerg Infect Dis 2003; 9(7): 815-21.
[http://dx.doi.org/10.3201/eid0907.030065] [PMID: 12890321]
[3]
Sissons J, Alsam S, Jayasekera S, Kim KS, Stins M, Khan NA. Acanthamoeba induces cell-cycle arrest in host cells. J Med Microbiol 2004; 53(8): 711-7.
[http://dx.doi.org/10.1099/jmm.0.45604-0] [PMID: 15272056]
[4]
Martinez A. Free-Living Amebas: Naegleria, Acanthamoeba and Balamuthia. In: Baron S, Ed. Medical Microbiology. (4th ed.), Galveston, TX: University of Texas Medical Branch at Galveston 1996.
[5]
Badirzadeh A, Niyyati M, Babaei Z, Amini H, Badirzadeh H, Rezaeian M. Isolation of free-living amoebae from sarein hot springs in ardebil province, Iran. Iran J Parasitol 2011; 6(2): 1-8.
[PMID: 22347281]
[6]
Mazur T. Hadaś E, Iwanicka I. The duration of the cyst stage and the viability and virulence of Acanthamoeba isolates. Trop Med Parasitol 1995; 46(2): 106-8.
[PMID: 8525280]
[7]
Ikeda Y, Miyazaki D, Yakura K, et al. Assessment of real-time polymerase chain reaction detection of Acanthamoeba and prognosis determinants of Acanthamoeba keratitis. Ophthalmology 2012; 119(6): 1111-9.
[http://dx.doi.org/10.1016/j.ophtha.2011.12.023] [PMID: 22381810]
[8]
Alexander CL, Coyne M, Jones B, Anijeet D. Acanthamoeba keratitis: improving the Scottish diagnostic service for the rapid molecular detection of Acanthamoeba species. J Med Microbiol 2015; 64(7): 682-7.
[http://dx.doi.org/10.1099/jmm.0.000086] [PMID: 25976006]
[9]
Khairnar K, Tamber GS, Ralevski F, Pillai DR. Comparison of molecular diagnostic methods for the detection of Acanthamoeba spp. from clinical specimens submitted for keratitis. Diagn Microbiol Infect Dis 2011; 70(4): 499-506.
[http://dx.doi.org/10.1016/j.diagmicrobio.2011.03.019] [PMID: 21658877]
[10]
Walochnik J, Scheikl U, Haller-Schober EM. Twenty years of acanthamoeba diagnostics in Austria. J Eukaryot Microbiol 2015; 62(1): 3-11.
[http://dx.doi.org/10.1111/jeu.12149] [PMID: 25047131]
[11]
Pussard MJP, Pons R. Morphology of the cyst wall and taxonomy of the genus Acanthamoeba (Protozoa, Amoebida). Protistologica 1977; 13: 557-98.
[12]
Page FC. A new key to freshwater and soil gymnamoebae: with instructions for culture: Freshwater biological association. CCAP 1989; 153: 55-6.
[13]
Lorenzo-Morales J, Monteverde-Miranda CA, Jiménez C, Tejedor ML, Valladares B, Ortega-Rivas A. Evaluation of Acanthamoeba isolates from environmental sources in Tenerife, Canary Islands, Spain. Ann Agric Environ Med 2005; 12(2): 233-6.
[PMID: 16457479]
[14]
Marciano-Cabral F, Cabral G. Acanthamoeba spp. as agents of disease in humans. Clin Microbiol Rev 2003; 16(2): 273-307.
[http://dx.doi.org/10.1128/CMR.16.2.273-307.2003] [PMID: 12692099]
[15]
Schuster FL, Visvesvara GS. Free-living amoebae as opportunistic and non-opportunistic pathogens of humans and animals. Int J Parasitol 2004; 34(9): 1001-27.
[http://dx.doi.org/10.1016/j.ijpara.2004.06.004] [PMID: 15313128]
[16]
Lim N, Goh D, Bunce C, et al. Comparison of polyhexamethylene biguanide and chlorhexidine as monotherapy agents in the treatment of Acanthamoeba keratitis. Am J Ophthalmol 2008; 145(1): 130-5.
[http://dx.doi.org/10.1016/j.ajo.2007.08.040] [PMID: 17996208]
[17]
Martín-Navarro CM, Lorenzo-Morales J, Cabrera-Serra MG, et al. The potential pathogenicity of chlorhexidine-sensitive Acanthamoeba strains isolated from contact lens cases from asymptomatic individuals in Tenerife, Canary Islands, Spain. J Med Microbiol 2008; 57(11): 1399-404.
[http://dx.doi.org/10.1099/jmm.0.2008/003459-0] [PMID: 18927419]
[18]
Lee JE, Oum BS, Choi HY, Yu HS, Lee JS. Cysticidal effect on acanthamoeba and toxicity on human keratocytes by polyhexamethylene biguanide and chlorhexidine. Cornea 2007; 26(6): 736-41.
[http://dx.doi.org/10.1097/ICO.0b013e31805b7e8e] [PMID: 17592327]
[19]
Ferrari G, Matuska S, Rama P. Double-biguanide therapy for resistant Acanthamoeba keratitis. Case Rep Ophthalmol 2011; 2(3): 338-42.
[http://dx.doi.org/10.1159/000334270] [PMID: 22174703]
[20]
Itahashi M, Higaki S, Fukuda M, Mishima H, Shimomura Y. Utility of real-time polymerase chain reaction in diagnosing and treating Acanthamoeba keratitis. Cornea 2011; 30(11): 1233-7.
[http://dx.doi.org/10.1097/ICO.0b013e3182032196] [PMID: 21955634]
[21]
Thakkar KN, Mhatre SS, Parikh RY. Biological synthesis of metallic nanoparticles. Nanomedicine 2010; 6(2): 257-62.
[http://dx.doi.org/10.1016/j.nano.2009.07.002] [PMID: 19616126]
[22]
Siddique S, Chow JCL. Gold nanoparticles for drug delivery and cancer therapy. Appl Sci 2020; 10(11): 3824.
[http://dx.doi.org/10.3390/app10113824]
[23]
Farzin A, Etesami SA, Quint J, Memic A, Tamayol A. Tamayol, AJAHM. Magnetic nanoparticles in cancer therapy and diagnosis. Adv Healthc Mater 2020; 9(9): 1901058.
[http://dx.doi.org/10.1002/adhm.201901058] [PMID: 32196144]
[24]
Banik BL, Fattahi P, Brown JL. Polymeric nanoparticles: the future of nanomedicine. Wiley Interdiscip Rev Nanomed Nanobiotechnol 2016; 8(2): 271-99.
[http://dx.doi.org/10.1002/wnan.1364] [PMID: 26314803]
[25]
Anwar A, Siddiqui R, Shah MR, Khan NA. Gold nanoparticle-conjugated cinnamic acid exhibits antiacanthamoebic and antibacterial properties. Antimicrob Agents Chemother 2018; 62(9): e00630-18.
[http://dx.doi.org/10.1128/AAC.00630-18] [PMID: 29967024]
[26]
Anwar A, Siddiqui R, Shah M, Khan N. Gold nanoparticles conjugation enhances antiacanthamoebic properties of nystatin, fluconazole and amphotericin B. J Microbiol Biotechnol 2019; 29(1): 171-7.
[http://dx.doi.org/10.4014/jmb.1805.05028] [PMID: 30415525]
[27]
Walvekar S, Anwar A, Anwar A, et al. Conjugation with silver nanoparticles enhances anti-acanthamoebic activity of Kappaphycus alvarezii. J Parasitol 2021; 107(4): 537-46.
[http://dx.doi.org/10.1645/21-41] [PMID: 34265050]
[28]
Grün AL, Scheid P. Haurِder B, Emmerling C, Manz W. Assessment of the effect of silver nanoparticles on the relevant soil protozoan genus Acanthamoeba. J Plant Nutr Soil Sci 2017; 180(5): 602-13.
[http://dx.doi.org/10.1002/jpln.201700277]
[29]
Anwar A, Abdalla SAO, Aslam Z, Shah MR, Siddiqui R, Khan NA. Oleic acid–conjugated silver nanoparticles as efficient antiamoebic agent against Acanthamoeba castellanii. Parasitol Res 2019; 118(7): 2295-304.
[http://dx.doi.org/10.1007/s00436-019-06329-3] [PMID: 31093751]
[30]
Padzik M, Hendiger EB, Chomicz L, et al. Tannic acid-modified silver nanoparticles as a novel therapeutic agent against Acanthamoeba. Parasitol Res 2018; 117(11): 3519-25.
[http://dx.doi.org/10.1007/s00436-018-6049-6] [PMID: 30112674]
[31]
Masri A, Abdelnasir S, Anwar A, et al. Antimicrobial properties of multifunctional polypyrrole-cobalt oxide-silver nanocomposite against pathogenic bacteria and parasite. Appl Microbiol Biotechnol 2021; 105(8): 3315-25.
[http://dx.doi.org/10.1007/s00253-021-11221-1] [PMID: 33797573]
[32]
Anwar A, Ting ELS, Anwar A, et al. Antiamoebic activity of plant-based natural products and their conjugated silver nanoparticles against Acanthamoeba castellanii (ATCC 50492). AMB Express 2020; 10(1): 24.
[http://dx.doi.org/10.1186/s13568-020-0960-9] [PMID: 32016777]
[33]
Kusrini E, Sabira K, Hashim F, et al. Design, synthesis and antiamoebic activity of dysprosium‐based nanoparticles using contact lenses as carriers against Acanthamoeba sp. Acta Ophthalmol 2021; 99(2): e178-88.
[http://dx.doi.org/10.1111/aos.14541] [PMID: 32701190]
[34]
Ziaei Hezarjaribi H, Toluee E, Saberi R, Dadi MY, Fakhar M, Akhtari J. In vitro anti-Acanthamoeba activity of the commercial chitosan and nano-chitosan against pathogenic Acanthamoeba genotype T4. J Parasit Dis 2021; 45(4): 921-9.
[http://dx.doi.org/10.1007/s12639-021-01380-3] [PMID: 34789973]
[35]
Elkadery AAS, Elsherif EA, Ezz Eldin HM, Fahmy IAF, Mohammad OS. Efficient therapeutic effect of Nigella sativa aqueous extract and chitosan nanoparticles against experimentally induced Acanthamoeba keratitis. Parasitol Res 2019; 118(8): 2443-54.
[http://dx.doi.org/10.1007/s00436-019-06359-x] [PMID: 31144032]
[36]
Abdelnasir S, Mungroo MR, Shahabuddin S, Siddiqui R, Khan NA, Anwar A. Polyaniline-conjugated boron nitride nanoparticles exhibiting potent effects against pathogenic brain-eating amoebae. ACS Chem Neurosci 2021; 12(19): 3579-87.
[http://dx.doi.org/10.1021/acschemneuro.1c00179] [PMID: 34545742]
[37]
Mahboob T, Nawaz M, Tian-Chye T, Samudi C, Wiart C, Nissapatorn V. Preparation of poly (dl-lactide-co-glycolide) nanoparticles encapsulated with periglaucine A and betulinic acid for in vitro anti-Acanthamoeba and cytotoxicity activities. Pathogens 2018; 7(3): 62.
[http://dx.doi.org/10.3390/pathogens7030062] [PMID: 30012991]
[38]
Mahboob T, Nawaz M, de Lourdes Pereira M, et al. PLGA nanoparticles loaded with Gallic acid-a constituent of Leea indica against Acanthamoeba triangularis. Sci Rep 2020; 10(1): 8954.
[http://dx.doi.org/10.1038/s41598-020-65728-0] [PMID: 32488154]
[39]
Panatieri LF, Brazil NT, Faber K, et al. Nanoemulsions containing a coumarin-rich extract from Pterocaulon balansae (Asteraceae) for the treatment of ocular Acanthamoeba keratitis. AAPS PharmSciTech 2017; 18(3): 721-8.
[http://dx.doi.org/10.1208/s12249-016-0550-y] [PMID: 27225384]
[40]
Aqeel Y, Siddiqui R, Anwar A, Shah MR, Khan NA. Gold nanoparticle conjugation enhances the antiacanthamoebic effects of chlorhexidine. Chemother 2016; 60(3): 1283-8.
[41]
Niyyati M, Sasani R, Mohebali M, et al. Anti-Acanthamoeba effects of silver and gold nanoparticles and contact lenses disinfection solutions. Iran J Parasitol 2018; 13(2): 180-5.
[PMID: 30069201]
[42]
Padzik M, Hendiger EB, Żochowska EA, et al. Evaluation of in vitro effect of selected contact lens solutions conjugated with nanoparticles in terms of preventive approach to public health risk generated by Acanthamoeba strains. Ann Agric Environ Med 2019; 26(1): 198-202.
[http://dx.doi.org/10.26444/aaem/105394] [PMID: 30922053]
[43]
Anwar A, Soomaroo A, Anwar A, Siddiqui R, Khan NA. Metformin-coated silver nanoparticles exhibit anti-acanthamoebic activities against both trophozoite and cyst stages. Exp Parasitol 2020; 215: 107915.
[http://dx.doi.org/10.1016/j.exppara.2020.107915] [PMID: 32461112]
[44]
Anwar A, Siddiqui R, Hussain MA, Ahmed D, Shah MR. Silver nanoparticle conjugation affects antiacanthamoebic activities of amphotericin B, nystatin, and fluconazole. Parasitol Res 2018; 117(1): 265-71.
[45]
Hendiger EB, Padzik M, Sifaoui I, et al. Silver nanoparticles conjugated with contact lens solutions may reduce the risk of Acanthamoeba keratitis. Pathogens 2021; 10(5): 583.
[http://dx.doi.org/10.3390/pathogens10050583] [PMID: 34064555]
[46]
Anwar A, Yi YP, Fatima I, et al. Antiamoebic activity of synthetic tetrazoles against Acanthamoeba castellanii belonging to T4 genotype and effects of conjugation with silver nanoparticles. Parasitol Res 2020; 119(6): 1943-54.
[http://dx.doi.org/10.1007/s00436-020-06694-4] [PMID: 32385711]
[47]
Anwar A, Rajendran K, Siddiqui R, Raza Shah M, Khan NA. Clinically approved drugs against CNS diseases as potential therapeutic agents to target brain-eating amoebae. ACS Chem Neurosci 2019; 10(1): 658-66.
[http://dx.doi.org/10.1021/acschemneuro.8b00484] [PMID: 30346711]
[48]
Abdelnasir S, Anwar A, Kawish M, et al. Metronidazole conjugated magnetic nanoparticles loaded with amphotericin B exhibited potent effects against pathogenic Acanthamoeba castellanii belonging to the T4 genotype. AMB Express 2020; 10(1): 127.
[http://dx.doi.org/10.1186/s13568-020-01061-z] [PMID: 32681358]
[49]
Iqbal K, Abdalla SAO, Anwar A, et al. Isoniazid conjugated magnetic nanoparticles loaded with Amphotericin B as a potent antiamoebic agent against Acanthamoeba castellanii. Antibiotics 2020; 9(5): 276.
[http://dx.doi.org/10.3390/antibiotics9050276] [PMID: 32466210]
[50]
Imran M, Muazzam AG, Habib A, Matin A. Synthesis, characterization and amoebicidal potential of locally synthesized TiO2 nanoparticles against pathogenic Acanthamoeba trophozoites in vitro. J Photochem Photobiol B 2016; 159: 125-32.
[http://dx.doi.org/10.1016/j.jphotobiol.2016.03.014] [PMID: 27054875]
[51]
Goldberg M, Langer R, Jia X. Nanostructured materials for applications in drug delivery and tissue engineering. J Biomater Sci Polym Ed 2007; 18(3): 241-68.
[http://dx.doi.org/10.1163/156856207779996931] [PMID: 17471764]
[52]
Patra JK, Das G, Fraceto LF, et al. Nano based drug delivery systems: recent developments and future prospects. J Nanobiotechnology 2018; 16(1): 71.
[http://dx.doi.org/10.1186/s12951-018-0392-8] [PMID: 30231877]
[53]
Ramalingam B, Parandhaman T, Das SK. Antibacterial effects of biosynthesized silver nanoparticles on surface ultrastructure and nanomechanical properties of gram-negative bacteria viz. Escherichia coli and Pseudomonas aeruginosa. ACS Appl Mater Interfaces 2016; 8(7): 4963-76.
[http://dx.doi.org/10.1021/acsami.6b00161] [PMID: 26829373]
[54]
Leung YH, Ng AMC, Xu X, et al. Mechanisms of antibacterial activity of MgO: non-ROS mediated toxicity of MgO nanoparticles towards Escherichia coli. Small 2014; 10(6): 1171-83.
[http://dx.doi.org/10.1002/smll.201302434] [PMID: 24344000]
[55]
Jung WK, Koo HC, Kim KW, Shin S, Kim SH, Park YH. Antibacterial activity and mechanism of action of the silver ion in Staphylococcus aureus and Escherichia coli. Appl Environ Microbiol 2008; 74(7): 2171-8.
[http://dx.doi.org/10.1128/AEM.02001-07] [PMID: 18245232]
[56]
Wang L, Hu C, Shao L. The antimicrobial activity of nanoparticles: present situation and prospects for the future. Int J Nanomedicine 2017; 12: 1227-49.
[http://dx.doi.org/10.2147/IJN.S121956] [PMID: 28243086]
[57]
Cirri M, Mennini N, Maestrelli F, Mura P, Ghelardini C, Di Cesare Mannelli L. Development and in vivo evaluation of an innovative “Hydrochlorothiazide-in cyclodextrins-in solid lipid nanoparticles” formulation with sustained release and enhanced oral bioavailability for potential hypertension treatment in pediatrics. Int J Pharm 2017; 521(1-2): 73-83.
[http://dx.doi.org/10.1016/j.ijpharm.2017.02.022] [PMID: 28229944]
[58]
Zinjarde SS. Bio-inspired nanomaterials and their applications as antimicrobial agents. Chronicles Young Sci 2012; 3(1): 74.
[http://dx.doi.org/10.4103/2229-5186.94314]
[59]
Kishore V, Yarla N, Bishayee A, et al. Multi-targeting andrographolide and its natural analogs as potential therapeutic agents. Curr Top Med Chem 2017; 17(8): 845-57.
[http://dx.doi.org/10.2174/1568026616666160927150452] [PMID: 27697058]
[60]
Shahrajabian MH, Sun W, Cheng Q. Exploring Artemisia annua L., artemisinin and its derivatives, from traditional Chinese wonder medicinal science. Not Bot Horti Agrobot Cluj-Napoca 2020; 48(4): 1719-41.
[http://dx.doi.org/10.15835/nbha48412002]
[61]
Parihar A, Parihar DS, Ranjan P, Khan R. Role of microfluidics-based point-of-care testing (POCT) for clinical applications Advanced Microfluidics-Based Point-of-Care Diagnostics In. CRC Press: Florida: Florida 2022; pp. 39-60.
[http://dx.doi.org/10.1201/9781003033479-2]
[62]
Al-Ardi MH, Health G. The uses of gold nanoparticles and Citrullus colocynthis L. nanoparticles against Giardia lamblia in vivo. Clin Epidemiol Glob Health 2020; 8(4): 1282-6.
[http://dx.doi.org/10.1016/j.cegh.2020.04.028]
[63]
Bavand Z, Gholami S, Honari S, Esboei B, Torabi N, Borabadi HJ. Effect of gold nanoparticles on Giardia lamblia cyst stage in in vitro. J Arak Univ Med Sci 2014; 16(10): 27-37.
[64]
Connor EE, Mwamuka J, Gole A, Murphy CJ, Wyatt MD. Gold nanoparticles are taken up by human cells but do not cause acute cytotoxicity. Small 2005; 1(3): 325-7.
[http://dx.doi.org/10.1002/smll.200400093] [PMID: 17193451]
[65]
Rodrigues GR. López-Abarrategui C, de la Serna Gómez I, Dias SC, Otero-González AJ, Franco OL. Antimicrobial magnetic nanoparticles based-therapies for controlling infectious diseases. Int J Pharm 2019; 555: 356-67.
[http://dx.doi.org/10.1016/j.ijpharm.2018.11.043] [PMID: 30453018]
[66]
Niemirowicz-Laskowska K, Mystkowska J. Łysik D, et al. Antimicrobial and physicochemical properties of artificial saliva formulations supplemented with core-shell magnetic nanoparticles. Int J Mol Sci 2020; 21(6): 1979.
[http://dx.doi.org/10.3390/ijms21061979] [PMID: 32183193]
[67]
Jagadeeshan S, Parsanathan R. Nano-metal oxides for antibacterial activity. In: Advanced Nanostructured Materials for Environmental Remediation. Springer International Publishing: New York 2019; 80: p. 59-90.
[68]
Jahangiri A, Barghi L. Polymeric nanoparticles: review of synthesis methods and applications in drug delivery. J Adv Chem Pharm Mater 2018; 1(2): 38-47.
[69]
Noshirvani N, Ghanbarzadeh B, Rezaei Mokarram R, Hashemi M, Life S. Novel active packaging based on carboxymethyl cellulose-chitosan-ZnO NPs nanocomposite for increasing the shelf life of bread. Food Packag Shelf Life 2017; 11: 106-14.
[http://dx.doi.org/10.1016/j.fpsl.2017.01.010]
[70]
Lima AF, Amado IR, Pires LR. Poly (d, l-lactide-co-glycolide)(PLGA) nanoparticles Loaded with proteolipid protein (PLP)—Exploring a new administration route. Polymers 2020; 12(12): 3063.
[http://dx.doi.org/10.3390/polym12123063] [PMID: 33371329]
[71]
Koul O, Walia S, Dhaliwal G. Essential oils as green pesticides: potential and constraints. Biopestic Int 2008; 4(1): 63-84.
[72]
Heydari M, Bagheri MJ. The antimicrobial effects of hydro-extract of Mentha Piperita lamiaceae essential oil nanoemulsion on gram-negative bacteria of Escherichia coli: A laboratory study. Majallah-i Ilmi-i Danishgah-i Ulum-i Pizishki-i Rafsanjan 2019; 18(6): 515-28.

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