{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T07:27:46Z","timestamp":1790839666299,"version":"4.1.0"},"reference-count":29,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,5,5]],"date-time":"2022-05-05T00:00:00Z","timestamp":1651708800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico (CNPq, Brazil)","award":["425332\/2018-7"],"award-info":[{"award-number":["425332\/2018-7"]}]},{"name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico (CNPq, Brazil)","award":["305659\/2017-0"],"award-info":[{"award-number":["305659\/2017-0"]}]},{"name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico (CNPq, Brazil)","award":["306198\/2021-5"],"award-info":[{"award-number":["306198\/2021-5"]}]},{"name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico (CNPq, Brazil)","award":["401390\/2020-9"],"award-info":[{"award-number":["401390\/2020-9"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Liposomal amphotericin B (AmB) or AmBisome\u00ae is the most effective and safe therapeutic agent for visceral leishmaniasis (VL), but its clinical efficacy is limited in cutaneous leishmaniasis (CL) and HIV\/VL co-infection. The aim of this work was to develop a formulation of AmB in PEGylated liposomes and compare its efficacy to AmBisome\u00ae in a murine model of CL. Formulations of AmB in conventional and PEGylated liposomes were characterized for particle size and morphology, drug encapsulation efficiency and aggregation state. Those were compared to AmBisome\u00ae in Leishmania amazonensis-infected BALB\/c mice for their effects on the lesion size growth and parasite load. The conventional and PEGylated formulations showed vesicles with 100\u2013130 nm diameter and low polydispersity, incorporating more than 95% of AmB under the non-aggregated form. Following parenteral administration in the murine model of CL, the PEGylated formulation of AmB significantly reduced the lesion size growth and parasite load, in comparison to control groups, in contrast to conventional liposomal AmB. The PEGylated formulation of AmB was also effective when given by oral route on a 2-day regimen. This work reports for the first time that PEGylated liposomal AmB can improve the treatment of experimental cutaneous leishmaniasis by both parenteral and oral routes.<\/jats:p>","DOI":"10.3390\/pharmaceutics14050989","type":"journal-article","created":{"date-parts":[[2022,5,6]],"date-time":"2022-05-06T02:46:39Z","timestamp":1651805199000},"page":"989","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Formulation of Amphotericin B in PEGylated Liposomes for Improved Treatment of Cutaneous Leishmaniasis by Parenteral and Oral Routes"],"prefix":"10.3390","volume":"14","author":[{"given":"Guilherme S.","family":"Ramos","sequence":"first","affiliation":[{"name":"Department of Physiology and Biophysics, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virg\u00ednia M. R.","family":"Vallejos","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7360-8231","authenticated-orcid":false,"given":"Gabriel S. M.","family":"Borges","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raquel M.","family":"Almeida","sequence":"additional","affiliation":[{"name":"Department of Parasitology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Izabela M.","family":"Alves","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta M. G.","family":"Aguiar","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3905-3674","authenticated-orcid":false,"given":"Christian","family":"Fernandes","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4534-2779","authenticated-orcid":false,"given":"Pedro P. G.","family":"Guimar\u00e3es","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4713-575X","authenticated-orcid":false,"given":"Ricardo T.","family":"Fujiwara","sequence":"additional","affiliation":[{"name":"Department of Parasitology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8542-6793","authenticated-orcid":false,"given":"Philippe M.","family":"Loiseau","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Antiparasite Chemotherapy, UMR 8076 CNRS BioCIS, University Paris-Saclay, F-92296 Chatenay-Malabry, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucas A. M.","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3783-5717","authenticated-orcid":false,"given":"Fr\u00e9d\u00e9ric","family":"Fr\u00e9zard","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,5]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (WHO) (2020). Ending the Neglect to Attain the Sustainable Development Goals: A Road Map for Neglected Tropical Diseases 2021\u22122030, WHO."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1539","DOI":"10.1093\/cid\/ciw742","article-title":"Diagnosis and Treatment of Leishmaniasis: Clinical Practice Guidelines by the Infectious Diseases Society of America (IDSA) and the American Society of Tropical Medicine and Hygiene (ASTMH)","volume":"63","author":"Aronson","year":"2016","journal-title":"Clin. Infect. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Ubals, M., Bosch-Nicolau, P., S\u00e1nchez-Montalv\u00e1, A., Salvador, F., Aparicio-Espa\u00f1ol, G., Sulleiro, E., Silgado, A., Soriano-Arandes, A., Espiau, M., and Ferrer, B. (2021). Treatment of complex cutaneous leishmaniasis with liposomal amphotericin B. Pathogens, 10.","DOI":"10.3390\/pathogens10101253"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1056\/NEJMoa0903627","article-title":"Single-dose liposomal amphotericin B for visceral leishmaniasis in India","volume":"362","author":"Sundar","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1093\/cid\/civ416","article-title":"Treatment of disseminated leishmaniasis with liposomal amphotericin B","volume":"61","author":"Machado","year":"2015","journal-title":"Clin. Infect. Dis."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Guery, R., Henry, B., Martin-Blondel, G., Rouzaud, C., Cordoliani, F., Harms, G., Gangneux, J.P., Foulet, F., Bourrat, E., and Baccard, M. (2017). Liposomal amphotericin B in travelers with cutaneous and muco-cutaneous leishmaniasis: Not a panacea. PLoS Negl. Trop. Dis., 11.","DOI":"10.1371\/journal.pntd.0006094"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1111\/bjd.18964","article-title":"American cutaneous leishmaniasis in French Guiana: A retrospective comparison between liposomal amphotericin B and meglumine antimoniate","volume":"183","author":"Senchyna","year":"2020","journal-title":"Br. J. Dermatol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e02009-17","DOI":"10.1128\/AAC.02009-17","article-title":"Relation between skin pharmacokinetics and efficacy in amBisome treatment of murine cutaneous leishmaniasis","volume":"62","author":"Wijnant","year":"2018","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.ijpddr.2018.04.001","article-title":"Comparative efficacy, toxicity and biodistribution of the liposomal amphotericin B formulations Fungisome\u00ae and AmBisome\u00ae in murine cutaneous leishmaniasis","volume":"8","author":"Wijnant","year":"2018","journal-title":"Int. J. Parasitol. Drugs Drug Resist."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Cuddihy, G., Wasan, E.K., Di, Y., and Wasan, K.M. (2019). The Development of oral amphotericin B to treat systemic fungal and parasitic infections: Has the myth been finally realized?. Pharmaceutics, 11.","DOI":"10.3390\/pharmaceutics11030099"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1080\/17425247.2019.1659243","article-title":"Recent advances in amphotericin B delivery strategies for the treatment of leishmaniases","volume":"16","author":"Lanza","year":"2019","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1086\/600105","article-title":"Highly effective oral amphotericin B formulation against murine visceral leishmaniasis","volume":"200","author":"Wasan","year":"2009","journal-title":"J. Infect. Dis."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Wasan, E.K., Gershkovich, P., Zhao, J., Zhu, X., Werbovetz, K., Tidwell, R.R., Clement, J.G., Thornton, S.J., and Wasan, K.M. (2010). A novel tropically stable oral amphotericin B formulation (iCo-010) exhibits efficacy against visceral leishmaniasis in a murine model. PLoS Negl. Trop. Dis., 4.","DOI":"10.1371\/journal.pntd.0000913"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1093\/infdis\/jir735","article-title":"An oral formulation of amphotericin B attached to functionalized carbon nanotubes is an effective treatment for experimental visceral leishmaniasis","volume":"205","author":"Prajapati","year":"2012","journal-title":"J. Infect. Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1021\/mp500527x","article-title":"Oral particle uptake and organ targeting drives the activity of amphotericin B nanoparticles","volume":"12","author":"Serrano","year":"2015","journal-title":"Mol. Pharm."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1080\/21691401.2018.1430699","article-title":"Design of mannosylated oral amphotericin B nanoformulation: Efficacy and safety in visceral leishmaniasis","volume":"46","author":"Sarwar","year":"2018","journal-title":"Artif. Cells Nanomed. Biotechnol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1038\/ja.2011.83","article-title":"Simultaneous determination of purity and potency of amphotericin B by HPLC","volume":"64","author":"Chang","year":"2011","journal-title":"J. Antibiot."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1080\/1061186X.2017.1387787","article-title":"A new nanoemulsion formulation improves antileishmanial activity and reduces toxicity of amphotericin B","volume":"26","author":"Santos","year":"2018","journal-title":"J. Drug Target."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.ejps.2015.01.015","article-title":"Nanoemulsions loaded with amphotericin B: A new approach for the treatment of leishmaniasis","volume":"70","author":"Caldeira","year":"2015","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3077","DOI":"10.1007\/s00436-019-06419-2","article-title":"Combination oral therapy against Leishmania amazonensis infection in BALB\/c mice using nanoassemblies made from amphiphilic antimony(V) complex incorporating miltefosine","volume":"118","author":"Carregal","year":"2019","journal-title":"Parasitol. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/S0301-4622(99)00009-5","article-title":"Thermodynamic and spectroscopic features of the behavior of amphotericin B in aqueous medium","volume":"77","author":"Romanini","year":"1999","journal-title":"Biophys. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1093\/mmy\/myv111","article-title":"Comparison between liposomal formulations of amphotericin B","volume":"54","author":"Gangneux","year":"2016","journal-title":"Med. Mycol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/0304-4157(92)90038-C","article-title":"Sterically stabilized liposomes","volume":"1113","author":"Woodle","year":"1992","journal-title":"Biochim. Biophys. Acta-Rev. Biomembr."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Klein, M.E., Rieckmann, M., Sedding, D., Hause, G., Meister, A., M\u00e4der, K., and Lucas, H. (2021). Towards the development of long circulating phosphatidylserine (PS)- and phosphatidylglycerol (PG)-enriched anti-Inflammatory liposomes: Is PEGylation Effective?. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13020282"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1551","DOI":"10.1517\/17425247.2014.932347","article-title":"Mixed formulation of conventional and pegylated liposomes as a novel drug delivery strategy for improved treatment of visceral leishmaniasis","volume":"11","author":"Azevedo","year":"2014","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e00234-20","DOI":"10.1128\/AAC.00234-20","article-title":"Therapeutic Efficacy of a Mixed Formulation of Conventional and PEGylated Liposomes Containing Meglumine Antimoniate, Combined with Allopurinol, in Dogs Naturally Infected with Leishmania infantum","volume":"64","author":"Ramos","year":"2020","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"4103819","DOI":"10.1155\/2019\/4103819","article-title":"Sex-Related Differences in Immune Response and Symptomatic Manifestations to Infection with Leishmania Species","volume":"2019","author":"Lockard","year":"2019","journal-title":"J. Immunol. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e02525-16","DOI":"10.1128\/AAC.02525-16","article-title":"Biodistribution and in vivo antileishmanial activity of 1,2-distigmasterylhemisuccinoyl-sn-glycero-3-phosphocholine liposome-Intercalated amphotericin B","volume":"61","author":"Iman","year":"2017","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_29","first-page":"7265","article-title":"Physical characterization and in vivo pharmacokinetic study of self-assembling amphotericin B-loaded lecithin-based mixed polymeric micelles","volume":"10","author":"Chen","year":"2015","journal-title":"Int. J. Nanomed."}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/14\/5\/989\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:06:19Z","timestamp":1760137579000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/14\/5\/989"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,5]]},"references-count":29,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2022,5]]}},"alternative-id":["pharmaceutics14050989"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics14050989","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,5]]}}}