{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T04:00:42Z","timestamp":1790654442623,"version":"4.1.0"},"update-to":[{"DOI":"10.1371\/journal.pntd.0012127","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2024,4,26]],"date-time":"2024-04-26T00:00:00Z","timestamp":1714089600000}}],"reference-count":45,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2024,4,16]],"date-time":"2024-04-16T00:00:00Z","timestamp":1713225600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","award":["001"],"award-info":[{"award-number":["001"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["151891\/2022-2"],"award-info":[{"award-number":["151891\/2022-2"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["301384\/2019-3"],"award-info":[{"award-number":["301384\/2019-3"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Cutaneous leishmaniasis (CL) is characterized by potentially disfiguring skin ulcers carrying significant social stigma. To mitigate systemic drug exposure and reduce the toxicity from available treatments, studies addressing new local therapeutic strategies using available medications are coming up. This review systematically compiles preclinical and clinical data on the efficacy of amphotericin B (AmB) administered locally for cutaneous leishmaniasis.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methodology<\/jats:title>\n<jats:p>Structured searches were conducted in major databases. Clinical studies reporting cure rates and preclinical studies presenting any efficacy outcome were included. Exclusion criteria comprised nonoriginal studies, <jats:italic>in vitro<\/jats:italic> investigations, studies with fewer than 10 treated patients, and those evaluating AmB in combination with other antileishmanial drug components.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Principal findings<\/jats:title>\n<jats:p>A total of 21 studies were identified, encompassing 16 preclinical and five clinical studies. Preclinical assessments generally involved the topical use of commercial AmB formulations, often in conjunction with carriers or controlled release systems. However, the variation in the treatment schedules hindered direct comparisons. In clinical studies, topical AmB achieved a pooled cure rate of 45.6% [CI: 27.5\u201364.8%; I2 = 79.7; p = 0.002), while intralesional (IL) administration resulted in a 69.8% cure rate [CI: 52.3\u201382.9%; I2 = 63.9; p = 0.06). In the direct comparison available, no significant difference was noted between AmB-IL and meglumine antimoniate-IL administration (OR:1.7; CI:0.34\u20139.15, I2 = 79.1; p = 0.00), however a very low certainty of evidence was verified.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>Different AmB formulations and administration routes have been explored in preclinical and clinical studies. Developing therapeutic technologies is evident. Current findings might be interpreted as a favorable proof of concept for the local AmB administration which makes this intervention eligible to be explored in future well-designed studies towards less toxic treatments for leishmaniasis.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pntd.0012127","type":"journal-article","created":{"date-parts":[[2024,4,16]],"date-time":"2024-04-16T18:28:10Z","timestamp":1713292090000},"page":"e0012127","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":16,"title":["Local amphotericin B therapy for Cutaneous Leishmaniasis: A systematic review"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5040-8870","authenticated-orcid":true,"given":"L\u00edndicy Leidicy","family":"Alves","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariana Louren\u00e7o","family":"Freire","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isadora Lana","family":"Troian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eliane de","family":"Morais-Teixeira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gl\u00e1ucia","family":"Cota","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,4,16]]},"reference":[{"key":"pntd.0012127.ref001","unstructured":"PAHO. Leishmanioses: Informe Epidemiol\u00f3gico das Am\u00e9ricas, No. 10 (Dezembro 2021). OPAS; 2021 Dec. Available: https:\/\/iris.paho.org\/handle\/10665.2\/55386"},{"key":"pntd.0012127.ref002","unstructured":"WHOb. Global leishmaniasis surveillance: 2021, assessing the impact of the COVID-19 pandemic. In: b [Internet]. 2022 [cited 5 Jun 2023]. Available: https:\/\/www.who.int\/publications\/i\/item\/who-wer9745-575-590"},{"key":"pntd.0012127.ref003","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1093\/trstmh\/trt021","article-title":"Assessment of the quality of life of patients with cutaneous leishmaniasis in Belo Horizonte, Brazil, 2009\u20132010. A pilot study","volume":"107","author":"AC de Castro Toledo","year":"2013","journal-title":"Trans R Soc Trop Med Hyg"},{"key":"pntd.0012127.ref004","doi-asserted-by":"crossref","first-page":"e0189906","DOI":"10.1371\/journal.pone.0189906","article-title":"The mosquitoes that destroy your faceSocial impact of Cutaneous Leishmaniasis in South-eastern Morocco, A qualitative study.","volume":"12","author":"I Bennis","year":"2017","journal-title":"PLoS One."},{"key":"pntd.0012127.ref005","doi-asserted-by":"crossref","first-page":"e0011029","DOI":"10.1371\/journal.pntd.0011029","article-title":"Cutaneous leishmaniasis treatment and therapeutic outcomes in special populations: A collaborative retrospective study.","volume":"17","author":"M Castro M del","year":"2023","journal-title":"PLoS Negl Trop Dis"},{"key":"pntd.0012127.ref006","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.riam.2009.06.003","article-title":"Amphotericin B: side effects and toxicity.","volume":"26","author":"R Laniado-Labor\u00edn","year":"2009","journal-title":"Rev Iberoam Micol"},{"key":"pntd.0012127.ref007","doi-asserted-by":"crossref","first-page":"417","DOI":"10.2147\/nano.2006.1.4.417","article-title":"Optimizing efficacy of amphotericin B through nanomodification.","volume":"1","author":"SP Vyas","year":"2006","journal-title":"Int J Nanomedicine"},{"key":"pntd.0012127.ref008","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1007\/s40265-013-0069-4","article-title":"Amphotericin B formulations: a comparative review of efficacy and toxicity.","volume":"73","author":"RJ Hamill","year":"2013","journal-title":"Drugs"},{"key":"pntd.0012127.ref009","volume-title":"Guideline for the Treatment of Leishmaniasis in the Americas.","author":"PAHO","year":"2022","edition":"2"},{"key":"pntd.0012127.ref010","first-page":"113","article-title":"Meglumine antimoniate intralesional infiltration for localised cutaneous leishmaniasis: a single arm, open label, phase II clinical trial","author":"DB Ramalho","year":"2018","journal-title":"Mem Inst Oswaldo Cruz"},{"key":"pntd.0012127.ref011","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1517\/17425247.2012.701204","article-title":"Drug delivery systems for the topical treatment of cutaneous leishmaniasis.","volume":"9","author":"G Carneiro","year":"2012","journal-title":"Expert Opin Drug Deliv"},{"key":"pntd.0012127.ref012","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1080\/14787210.2020.1731305","article-title":"Safety profile of meglumine antimoniate intralesional infiltration for cutaneous leishmaniasis.","volume":"18","author":"HJ Fernandes","year":"2020","journal-title":"Expert Rev Anti Infect Ther"},{"key":"pntd.0012127.ref013","doi-asserted-by":"crossref","DOI":"10.7326\/0003-4819-151-4-200908180-00136","article-title":"The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration","volume":"151","author":"A Liberati","year":"2009","journal-title":"Ann Intern Med"},{"key":"pntd.0012127.ref014","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13643-016-0384-4","article-title":"Rayyan-a web and mobile app for systematic reviews.","volume":"5","author":"M Ouzzani","year":"2016","journal-title":"Syst Rev."},{"key":"pntd.0012127.ref015","doi-asserted-by":"crossref","first-page":"e2130","DOI":"10.1371\/journal.pntd.0002130","article-title":"Methodology of clinical trials aimed at assessing interventions for cutaneous leishmaniasis.","volume":"7","author":"P Olliaro","year":"2013","journal-title":"PLoS Negl Trop Dis"},{"key":"pntd.0012127.ref016","volume-title":"Cochrane handbook for systematic reviews of interventions version 6.4.","author":"JPT Higgins","year":"2023"},{"key":"pntd.0012127.ref017","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1471-2288-14-43","article-title":"SYRCLE\u2019s risk of bias tool for animal studies.","volume":"14","author":"CR Hooijmans","year":"2014","journal-title":"BMC Med Res Methodol."},{"key":"pntd.0012127.ref018","author":"BS Wells","year":"2021","journal-title":"Ottawa Hospital Research Institute"},{"key":"pntd.0012127.ref019","unstructured":"GRADE. Handbook for grading quality of evidence and strength of recommendations. Updated October 2013. Sch\u00fcnemann H, Bro\u017cek J, Guyatt G, Oxman AD, editors. 2013."},{"key":"pntd.0012127.ref020","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.exppara.2016.02.010","article-title":"Evaluation of the in vivo leishmanicidal activity of amphotericin B emulgel: An alternative for the treatment of skin leishmaniasis","volume":"164","author":"IM Pinheiro","year":"2016","journal-title":"Exp Parasitol"},{"key":"pntd.0012127.ref021","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.ijpddr.2019.06.001","article-title":"Novel and safe single-dose treatment of cutaneous leishmaniasis with implantable amphotericin B-loaded microparticles","volume":"11","author":"AJ Sousa-Batista","year":"2019","journal-title":"Int J Parasitol Drugs Drug Resist"},{"key":"pntd.0012127.ref022","first-page":"e00807","article-title":"Gallic and ellagic acids are promising adjuvants to conventional amphotericin B for the treatment of cutaneous leishmaniasis","volume":"64","author":"M Alves MM de","year":"2020","journal-title":"Antimicrob Agents Chemother"},{"key":"pntd.0012127.ref023","doi-asserted-by":"crossref","first-page":"2647","DOI":"10.1021\/acsinfecdis.0c00293","article-title":"Ultradeformable lipid vesicles localize amphotericin B in the dermis for the treatment of infectious skin diseases.","volume":"6","author":"R Fern\u00e1ndez-Garc\u00eda","year":"2020","journal-title":"ACS Infect Dis"},{"key":"pntd.0012127.ref024","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1128\/AAC.41.4.752","article-title":"Activity of liposomal amphotericin B against experimental cutaneous leishmaniasis","volume":"41","author":"V Yardley","year":"1997","journal-title":"Antimicrob Agents Chemother"},{"key":"pntd.0012127.ref025","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1016\/j.trstmh.2010.08.010","article-title":"An amphotericin B-based drug for treating experimental Leishmania major infection","volume":"104","author":"KD Corware","year":"2010","journal-title":"Trans R Soc Trop Med Hyg"},{"key":"pntd.0012127.ref026","doi-asserted-by":"crossref","first-page":"8029","DOI":"10.1016\/j.biomaterials.2011.07.021","article-title":"Accelerated healing of cutaneous leishmaniasis in non-healing BALB\/c mice using water soluble amphotericin B-polymethacrylic acid.","volume":"32","author":"K Corware","year":"2011","journal-title":"Biomaterials"},{"key":"pntd.0012127.ref027","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.actatropica.2017.06.004","article-title":"Topical treatment with nanoliposomal Amphotericin B reduces early lesion growth but fails to induce cure in an experimental model of cutaneous leishmaniasis caused by Leishmania mexicana","volume":"173","author":"S Varikuti","year":"2017","journal-title":"Acta Trop"},{"key":"pntd.0012127.ref028","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s10544-018-0355-8","article-title":"Microneedle-based delivery of Amphotericin B for treatment of cutaneous Leishmaniasis","volume":"21","author":"AK Nguyen","year":"2019","journal-title":"Biomed Microdevices"},{"key":"pntd.0012127.ref029","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.ijpddr.2019.09.004","article-title":"Development of a topical liposomal formulation of Amphotericin B for the treatment of cutaneous leishmaniasis","volume":"11","author":"MR Jaafari","year":"2019","journal-title":"Int J Parasitol Drugs Drug Resist"},{"key":"pntd.0012127.ref030","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1208\/s12249-022-02435-1","article-title":"Evaluation of the Efficacy of Amphotericin B and Terbinafine Microemulsions and Their Combination on Cutaneous Leishmaniasis and Comparison with the Conventional Drug Form in BALB\/c Mice.","volume":"23","author":"Z Baharvandi","year":"2022","journal-title":"AAPS PharmSciTech."},{"key":"pntd.0012127.ref031","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1128\/AAC.26.5.745","article-title":"Development of topical treatment for cutaneous leishmaniasis caused by Leishmania major in experimental animals","volume":"26","author":"J El-On","year":"1984","journal-title":"Antimicrob Agents Chemother"},{"key":"pntd.0012127.ref032","doi-asserted-by":"crossref","first-page":"3092","DOI":"10.1128\/AAC.42.12.3092","article-title":"Efficacious topical treatment for murine cutaneous leishmaniasis with ethanolic formulations of amphotericin B","volume":"42","author":"S Frankenburg","year":"1998","journal-title":"Antimicrob Agents Chemother"},{"key":"pntd.0012127.ref033","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1007\/s13346-018-00603-0","article-title":"Amphotericin B-loaded nanoparticles for local treatment of cutaneous leishmaniasis.","volume":"9","author":"A Abu Ammar","year":"2019","journal-title":"Drug Deliv Transl Res"},{"key":"pntd.0012127.ref034","doi-asserted-by":"crossref","first-page":"118900","DOI":"10.1016\/j.ijpharm.2019.118900","article-title":"Topical treatment of cutaneous leishmaniasis with novel amphotericin B-miltefosine co-incorporated second generation ultra-deformable liposomes","volume":"573","author":"MJ Dar","year":"2020","journal-title":"Int J Pharm"},{"key":"pntd.0012127.ref035","first-page":"1","article-title":"Preparation and characterization of nanostructured lipid carriers for improved topical drug delivery: evaluation in cutaneous leishmaniasis and vaginal candidiasis animal models.","volume":"21","author":"A Riaz","year":"2020","journal-title":"AAPS PharmSciTech."},{"key":"pntd.0012127.ref036","first-page":"2011","article-title":"Efficacy of topical liposomal amphotericin B versus intralesional meglumine antimoniate (Glucantime) in the treatment of cutaneous leishmaniasis.","author":"P Layegh","year":"2011","journal-title":"J Parasitol Res"},{"key":"pntd.0012127.ref037","doi-asserted-by":"crossref","first-page":"658","DOI":"10.26719\/emhj.22.070","article-title":"Pilot study of safety and efficacy of topical liposomal amphotericin B for cutaneous leishmaniasis caused by Leishmania major in Islamic Republic of Iran.","volume":"28","author":"A Khamesipour","year":"2022","journal-title":"East Mediterr Health J."},{"key":"pntd.0012127.ref038","doi-asserted-by":"crossref","first-page":"627","DOI":"10.4103\/idoj.IDOJ_470_18","article-title":"Comparison of efficacy of two different concentrations of intralesional amphotericin B in the treatment of cutaneous leishmaniasis; A randomized controlled trial.","volume":"10","author":"P Goswami","year":"2019","journal-title":"Indian Dermatol Online J"},{"key":"pntd.0012127.ref039","doi-asserted-by":"crossref","first-page":"e0006653","DOI":"10.1371\/journal.pntd.0006653","article-title":"A phase II study to evaluate the safety and efficacy of topical 3% amphotericin B cream (Anfoleish) for the treatment of uncomplicated cutaneous leishmaniasis in Colombia.","volume":"12","author":"L L\u00f3pez","year":"2018","journal-title":"PLoS Negl Trop Dis"},{"key":"pntd.0012127.ref040","doi-asserted-by":"crossref","first-page":"631","DOI":"10.4103\/0019-5154.143571","article-title":"Efficacy of intralesional amphotericin B for the treatment of cutaneous leishmaniasis","volume":"59","author":"VM Goyonlo","year":"2014","journal-title":"Indian J Dermatol"},{"key":"pntd.0012127.ref041","doi-asserted-by":"crossref","first-page":"e0184777","DOI":"10.1371\/journal.pone.0184777","article-title":"Efficacy of pentavalent antimoniate intralesional infiltration therapy for cutaneous leishmaniasis: A systematic review.","volume":"12","author":"NC Brito","year":"2017","journal-title":"PLoS One."},{"key":"pntd.0012127.ref042","unstructured":"Who. Leishmaniasis. 2023 [cited 5 Jun 2023] p. a. Available: https:\/\/www.who.int\/health-topics\/leishmaniasis#tab=tab_1"},{"key":"pntd.0012127.ref043","doi-asserted-by":"crossref","first-page":"e3000410","DOI":"10.1371\/journal.pbio.3000410","article-title":"The ARRIVE guidelines 2.0: Updated guidelines for reporting animal research","volume":"18","author":"NP du Sert","year":"2020","journal-title":"PLoS Biol"},{"key":"pntd.0012127.ref044","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/j.clindermatol.2006.05.008","article-title":"Cutaneous leishmaniasis.","volume":"25","author":"MS Bailey","year":"2007","journal-title":"Clin Dermatol"},{"key":"pntd.0012127.ref045","doi-asserted-by":"crossref","first-page":"e0149697","DOI":"10.1371\/journal.pone.0149697","article-title":"The cure rate after placebo or no therapy in American cutaneous leishmaniasis: a systematic review and meta-analysis.","volume":"11","author":"GF Cota","year":"2016","journal-title":"PLoS One."}],"updated-by":[{"DOI":"10.1371\/journal.pntd.0012127","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2024,4,26]],"date-time":"2024-04-26T00:00:00Z","timestamp":1714089600000}}],"container-title":["PLOS Neglected Tropical Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pntd.0012127","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,26]],"date-time":"2024-04-26T17:43:23Z","timestamp":1714153403000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pntd.0012127"}},"subtitle":[],"editor":[{"given":"Ana Laura","family":"Grossi de Oliveira","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2024,4,16]]},"references-count":45,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2024,4,16]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pntd.0012127","relation":{"new_version":[{"id-type":"doi","id":"10.1371\/journal.pntd.0012127","asserted-by":"object"}]},"ISSN":["1935-2735"],"issn-type":[{"value":"1935-2735","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,16]]}}}