{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T12:05:04Z","timestamp":1778501104827,"version":"3.51.4"},"reference-count":29,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2023,5,25]],"date-time":"2023-05-25T00:00:00Z","timestamp":1684972800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Union\u2019s Horizon"},{"name":"Research Council United Kingdom Grand Challenges Research","award":["MR\/P027989\/1"],"award-info":[{"award-number":["MR\/P027989\/1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,7,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>Cutaneous leishmaniasis (CL) is a neglected tropical disease causing a range of skin lesions for which safe and efficacious drugs are lacking. Oleylphosphocholine (OLPC) is structurally similar to miltefosine and has previously demonstrated potent activity against visceral leishmaniasis. We here present the in vitro and in vivo efficacy of OLPC against CL-causing Leishmania species.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>The antileishmanial activities of OLPC were evaluated and compared with miltefosine in vitro against intracellular amastigotes of seven CL-causing species. Following the confirmation of significant in vitro activity, the performance of the maximum tolerated dose of OLPC was evaluated in an experimental murine model of CL followed by a dose\u2013response titration and the efficacy evaluation of four OLPC formulations (two with a fast-release and two with a slow-release profile) using bioluminescent Leishmania major parasites.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>OLPC demonstrated potent in vitro activity of the same order as miltefosine in the intracellular macrophage model against a range of CL-causing species. A dose of 35 mg of OLPC\/kg\/day administered orally for 10 days was well-tolerated and able to reduce the parasite load in the skin of L. major-infected mice to a similar extent as the positive control paromomycin (50 mg\/kg\/day, intraperitoneally) in both in vivo studies. Reducing the dose of OLPC resulted in inactivity and modifying the release profile using mesoporous silica nanoparticles led to a decrease in activity when solvent-based loading was used in contrast to extrusion-based loading, which had no impact on its antileishmanial efficacy.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Together, these data suggest that OLPC could be a promising alternative to miltefosine treatment for CL. Further investigations exploring experimental models with additional Leishmania species and skin pharmacokinetic and dynamic analyses are required.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jac\/dkad162","type":"journal-article","created":{"date-parts":[[2023,5,25]],"date-time":"2023-05-25T19:41:19Z","timestamp":1685043679000},"page":"1723-1731","source":"Crossref","is-referenced-by-count":2,"title":["Efficacy of oleylphosphocholine in experimental cutaneous leishmaniasis"],"prefix":"10.1093","volume":"78","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8583-5282","authenticated-orcid":false,"given":"Katrien","family":"Van Bocxlaer","sequence":"first","affiliation":[{"name":"Department of Biology, York Biomedical Research Institute, University of York , York , UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jodie","family":"Dixon","sequence":"additional","affiliation":[{"name":"Department of Biology, York Biomedical Research Institute, University of York , York , UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johannes J","family":"Platteeuw","sequence":"additional","affiliation":[{"name":"Avivia BV, Novio Tech Campus , Nijmegen , The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dennie","family":"Van Den Heuvel","sequence":"additional","affiliation":[{"name":"Avivia BV, Novio Tech Campus , Nijmegen , The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kerri-Nicola","family":"Mcarthur","sequence":"additional","affiliation":[{"name":"Pharmidex Pharmaceutical Services Ltd. , London , UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andy","family":"Harris","sequence":"additional","affiliation":[{"name":"Pharmidex Pharmaceutical Services Ltd. , London , UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mo","family":"Alavijeh","sequence":"additional","affiliation":[{"name":"Pharmidex Pharmaceutical Services Ltd. , London , UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simon L","family":"Croft","sequence":"additional","affiliation":[{"name":"London School of Hygiene & Tropical Medicine, Faculty of Infectious and Tropical Diseases , London , UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vanessa","family":"Yardley","sequence":"additional","affiliation":[{"name":"London School of Hygiene & Tropical Medicine, Faculty of Infectious and Tropical Diseases , London , UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2023,5,25]]},"reference":[{"key":"2023070504554196400_dkad162-B1","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0035671","article-title":"Leishmaniasis worldwide and global estimates of its incidence","volume":"7","author":"Alvar","year":"2012","journal-title":"PloS One"},{"key":"2023070504554196400_dkad162-B2","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1016\/S0140-6736(18)31204-2","article-title":"Leishmaniasis","volume":"392","author":"Burza","year":"2018","journal-title":"Lancet"},{"key":"2023070504554196400_dkad162-B3","doi-asserted-by":"crossref","first-page":"489","DOI":"10.4269\/ajtmh.15-0408","article-title":"Social and economic burden of human leishmaniasis","volume":"94","author":"Okwor","year":"2016","journal-title":"Am J Trop Med Hyg"},{"key":"2023070504554196400_dkad162-B4","doi-asserted-by":"crossref","first-page":"1478","DOI":"10.1111\/j.1469-0691.2011.03630.x","article-title":"Leishmaniasis chemotherapy\u2014challenges and opportunities","volume":"17","author":"Croft","year":"2011","journal-title":"Clin Microbiol Infect"},{"key":"2023070504554196400_dkad162-B5","first-page":"24","volume-title":"Drug Discovery for Leishmaniasis","author":"Mowbray","year":"2018"},{"key":"2023070504554196400_dkad162-B6","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/S0001-706X(01)00197-8","article-title":"Sensitivities of Leishmania species to hexadecylphosphocholine (miltefosine), ET-18-OCH(3) (edelfosine) and amphotericin B","volume":"81","author":"Escobar","year":"2002","journal-title":"Acta Trop"},{"key":"2023070504554196400_dkad162-B7","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1111\/jtm.12089","article-title":"Leishman recommendations for treatment of cutaneous and mucosal leishmaniasis in travelers, 2014","volume":"21","author":"Blum","year":"2014","journal-title":"J Travel Med"},{"key":"2023070504554196400_dkad162-B8","doi-asserted-by":"crossref","DOI":"10.1136\/bmjgh-2018-000709","article-title":"Why miltefosine\u2014a life-saving drug for leishmaniasis\u2014is unavailable to people who need it the most","volume":"3","author":"Sunyoto","year":"2018","journal-title":"BMJ Glob Health"},{"key":"2023070504554196400_dkad162-B9","doi-asserted-by":"crossref","DOI":"10.3389\/fsoc.2020.540478","article-title":"Antiparasitic drugs in the United States\u2013two roads to high prices","volume":"5","author":"Shahriar","year":"2020","journal-title":"Front Sociol"},{"key":"2023070504554196400_dkad162-B10","first-page":"189","article-title":"The impact of the priority review voucher on research and development for tropical diseases","volume":"36","author":"Aerts","year":"2022","journal-title":"Pharmaceut Med"},{"key":"2023070504554196400_dkad162-B11","doi-asserted-by":"crossref","first-page":"2707","DOI":"10.1093\/jac\/dks273","article-title":"Efficacy and tolerability of oleylphosphocholine (OlPC) in a laboratory model of visceral leishmaniasis","volume":"67","author":"Fortin","year":"2012","journal-title":"J Antimicrob Chemother"},{"key":"2023070504554196400_dkad162-B12","doi-asserted-by":"crossref","first-page":"1892","DOI":"10.1093\/jac\/dkw089","article-title":"Pharmacokinetics and pharmacodynamics of oleylphosphocholine in a hamster model of visceral leishmaniasis","volume":"71","author":"Fortin","year":"2016","journal-title":"J Antimicrob Chemother"},{"key":"2023070504554196400_dkad162-B13","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1007\/s00436-013-3638-2","article-title":"First study on efficacy and tolerability of a new alkylphosphocholine molecule (oleylphosphocholine\u2013OlPC) in the treatment of canine leishmaniosis due to Leishmania infantum","volume":"113","author":"Hern\u00e1ndez","year":"2014","journal-title":"Parasitol Res"},{"key":"2023070504554196400_dkad162-B14","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pntd.0003144","article-title":"Direct comparison of the efficacy and safety of oral treatments with oleylphosphocholine (OlPC) and miltefosine in a mouse model of L. major cutaneous leishmaniasis","volume":"8","author":"Fortin","year":"2014","journal-title":"PLoS Negl Trop Dis"},{"key":"2023070504554196400_dkad162-B15","doi-asserted-by":"crossref","first-page":"6262","DOI":"10.1021\/acs.cgd.2c00843","article-title":"Integral role of water in the solid-state behavior of the antileishmanial drug miltefosine","volume":"22","author":"Hall","year":"2022","journal-title":"Crys Growth Des"},{"key":"2023070504554196400_dkad162-B16","doi-asserted-by":"crossref","first-page":"950","DOI":"10.3390\/pharmaceutics13070950","article-title":"Mesoporous silica particles as drug delivery systems\u2014the state of the art in loading methods and the recent progress in analytical techniques for monitoring these processes","volume":"13","author":"Trzeciak","year":"2021","journal-title":"Pharmaceutics"},{"key":"2023070504554196400_dkad162-B17","doi-asserted-by":"crossref","DOI":"10.1128\/AAC.02419-17","article-title":"Topical treatment for cutaneous leishmaniasis: dermato-pharmacokinetic lead optimization of benzoxaboroles","volume":"62","author":"Van Bocxlaer","year":"2018","journal-title":"Antimicrob Agents Chemother"},{"key":"2023070504554196400_dkad162-B18","doi-asserted-by":"crossref","DOI":"10.1128\/AAC.02048-16","article-title":"Use of optical imaging technology in the validation of a new, rapid, cost-effective drug screen as part of a tiered in vivo screening paradigm for development of drugs to treat cutaneous leishmaniasis","volume":"61","author":"Caridha","year":"2017","journal-title":"Antimicrob Agents Chemother"},{"key":"2023070504554196400_dkad162-B19","doi-asserted-by":"crossref","first-page":"2576","DOI":"10.1093\/jac\/dks275","article-title":"Miltefosine: a review of its pharmacology and therapeutic efficacy in the treatment of leishmaniasis","volume":"67","author":"Dorlo","year":"2012","journal-title":"J Antimicrob Chemother"},{"key":"2023070504554196400_dkad162-B20","doi-asserted-by":"crossref","DOI":"10.1136\/bmj.g4665","article-title":"US incentive scheme for neglected diseases: a good idea gone wrong?","volume":"349","author":"Doshi","year":"2014","journal-title":"BMJ"},{"key":"2023070504554196400_dkad162-B21","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1093\/jac\/dkp500","article-title":"In vitro activity of anti-leishmanial drugs against Leishmania donovani is host cell dependent","volume":"65","author":"Seifert","year":"2010","journal-title":"J Antimicrob Chemother"},{"key":"2023070504554196400_dkad162-B22","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/0166-6851(84)90004-5","article-title":"Sterols of Leishmania species. Implications for biosynthesis","volume":"10","author":"Goad","year":"1984","journal-title":"Mol Biochem Parasitol"},{"key":"2023070504554196400_dkad162-B23","doi-asserted-by":"crossref","first-page":"201","DOI":"10.2307\/3280147","article-title":"Lipids of Leishmania promastigotes","volume":"65","author":"Beach","year":"1979","journal-title":"J Parasitol"},{"key":"2023070504554196400_dkad162-B24","doi-asserted-by":"crossref","DOI":"10.1128\/AAC.00829-19","article-title":"Pharmacokinetics and pharmacodynamics of the nitroimidazole DNDI-0690 in mouse models of cutaneous leishmaniasis","volume":"63","author":"Wijnant","year":"2019","journal-title":"Antimicrob Agents Chemother"},{"issue":"Suppl 1","key":"2023070504554196400_dkad162-B25","doi-asserted-by":"crossref","first-page":"S17","DOI":"10.1016\/j.trstmh.2006.02.010","article-title":"Development of miltefosine as an oral treatment for leishmaniasis","volume":"100","author":"Sindermann","year":"2006","journal-title":"Trans R Soc Trop Med Hyg"},{"key":"2023070504554196400_dkad162-B26","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1007\/BF00695989","article-title":"Distribution of hexadecylphosphocholine and octadecyl-methyl-glycero-3-phosphocholine in rat tissues during steady-state treatment","volume":"31","author":"Marschner","year":"1992","journal-title":"Cancer Chemother Pharmacol"},{"key":"2023070504554196400_dkad162-B27","doi-asserted-by":"crossref","DOI":"10.1016\/j.jpba.2021.114402","article-title":"Development and validation of an HPLC-MS\/MS method for the quantification of the anti-leishmanial drug miltefosine in human skin tissue","volume":"207","author":"Roseboom","year":"2022","journal-title":"J Pharm Biom Anal"},{"key":"2023070504554196400_dkad162-B28","doi-asserted-by":"crossref","DOI":"10.1128\/AAC.02198-16","article-title":"Pharmacokinetics of miltefosine in children and adults with cutaneous leishmaniasis","volume":"61","author":"Castro","year":"2017","journal-title":"Antimicrob Agents Chemother"},{"key":"2023070504554196400_dkad162-B29","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1111\/jphp.12548","article-title":"Topical formulations of miltefosine for cutaneous leishmaniasis in a BALB\/c mouse model","volume":"68","author":"Van Bocxlaer","year":"2016","journal-title":"J Pharm Pharmacol"}],"container-title":["Journal of Antimicrobial Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jac\/article-pdf\/78\/7\/1723\/50792286\/dkad162.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jac\/article-pdf\/78\/7\/1723\/50792286\/dkad162.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,5]],"date-time":"2023-07-05T08:10:17Z","timestamp":1688544617000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jac\/article\/78\/7\/1723\/7179900"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,25]]},"references-count":29,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2023,5,25]]},"published-print":{"date-parts":[[2023,7,5]]}},"URL":"https:\/\/doi.org\/10.1093\/jac\/dkad162","relation":{},"ISSN":["0305-7453","1460-2091"],"issn-type":[{"value":"0305-7453","type":"print"},{"value":"1460-2091","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2023,7]]},"published":{"date-parts":[[2023,5,25]]}}}