{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T19:34:32Z","timestamp":1791488072815,"version":"4.3.4"},"reference-count":125,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,12,28]],"date-time":"2022-12-28T00:00:00Z","timestamp":1672185600000},"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","award":["306198\/2021-5"],"award-info":[{"award-number":["306198\/2021-5"]}]},{"name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","award":["RED-00202-22"],"award-info":[{"award-number":["RED-00202-22"]}]},{"name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","award":["0424\/22"],"award-info":[{"award-number":["0424\/22"]}]},{"name":"Funda\u00e7\u00e3o de Amparo a Pesquisa do Estado de Minas Gerais","award":["306198\/2021-5"],"award-info":[{"award-number":["306198\/2021-5"]}]},{"name":"Funda\u00e7\u00e3o de Amparo a Pesquisa do Estado de Minas Gerais","award":["RED-00202-22"],"award-info":[{"award-number":["RED-00202-22"]}]},{"name":"Funda\u00e7\u00e3o de Amparo a Pesquisa do Estado de Minas Gerais","award":["0424\/22"],"award-info":[{"award-number":["0424\/22"]}]},{"name":"MCTI\/FINEP","award":["306198\/2021-5"],"award-info":[{"award-number":["306198\/2021-5"]}]},{"name":"MCTI\/FINEP","award":["RED-00202-22"],"award-info":[{"award-number":["RED-00202-22"]}]},{"name":"MCTI\/FINEP","award":["0424\/22"],"award-info":[{"award-number":["0424\/22"]}]},{"name":"CNPq","award":["306198\/2021-5"],"award-info":[{"award-number":["306198\/2021-5"]}]},{"name":"CNPq","award":["RED-00202-22"],"award-info":[{"award-number":["RED-00202-22"]}]},{"name":"CNPq","award":["0424\/22"],"award-info":[{"award-number":["0424\/22"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>The liposomal amphotericin B (AmB) formulation, AmBisome\u00ae, still represents the best therapeutic option for cutaneous and visceral leishmaniasis. However, its clinical efficacy depends on the patient\u2019s immunological status, the clinical manifestation and the endemic region. Moreover, the need for parenteral administration, its side effects and high cost significantly limit its use in developing countries. This review reports the progress achieved thus far toward the understanding of the mechanism responsible for the reduced toxicity of liposomal AmB formulations and the factors that influence their efficacy against leishmaniasis. It also presents the recent advances in the development of more effective liposomal AmB formulations, including topical and oral liposome formulations. The critical role of the AmB aggregation state and release rate in the reduction of drug toxicity and in the drug efficacy by non-invasive routes is emphasized. This paper is expected to guide future research and development of innovative liposomal formulations of AmB.<\/jats:p>","DOI":"10.3390\/pharmaceutics15010099","type":"journal-article","created":{"date-parts":[[2022,12,28]],"date-time":"2022-12-28T08:57:24Z","timestamp":1672217844000},"page":"99","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":100,"title":["Liposomal Amphotericin B for Treatment of Leishmaniasis: From the Identification of Critical Physicochemical Attributes to the Design of Effective Topical and Oral Formulations"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3783-5717","authenticated-orcid":false,"given":"Fr\u00e9d\u00e9ric","family":"Fr\u00e9zard","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":"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"}]},{"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"}]},{"given":"Guilherme S.","family":"Ramos","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\/0000-0002-6375-4251","authenticated-orcid":false,"given":"Thais T.","family":"Santos","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"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3505-9494","authenticated-orcid":false,"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"}]},{"given":"Helane L. O.","family":"De Morais","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":[[2022,12,28]]},"reference":[{"key":"ref_1","unstructured":"PAHO (2022, October 11). Pan American Health Organization: Leishmaniasis. Available online: https:\/\/www.paho.org\/en\/topics\/leishmaniasis."},{"key":"ref_2","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_3","doi-asserted-by":"crossref","first-page":"8965","DOI":"10.1007\/s00253-020-10856-w","article-title":"Recent advances and new strategies on leishmaniasis treatment","volume":"104","author":"Roatt","year":"2020","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_4","unstructured":"World Health Organization (WHO) (2022). WHO Guideline for the Treatment of Visceral Leishmaniasis in HIV Co-Infected Patients in East Africa and South-East Asia, World Health Organization."},{"key":"ref_5","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":"ref_6","doi-asserted-by":"crossref","first-page":"727","DOI":"10.4269\/ajtmh.19-0568","article-title":"Liposomal Amphotericin B Treatment and the Leishmaniases","volume":"101","author":"Berman","year":"2019","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_7","unstructured":"PAHO (2022). Pan American Health Organization. Guideline for the Treatment of Leishmaniasis in the Americas, PAHO. [2nd ed.]."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2317","DOI":"10.3390\/molecules14072317","article-title":"Pentavalent antimonials: New perspectives for old drugs","volume":"14","author":"Demicheli","year":"2009","journal-title":"Molecules"},{"key":"ref_9","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_10","doi-asserted-by":"crossref","first-page":"660183","DOI":"10.3389\/fimmu.2021.660183","article-title":"Host-Directed Therapies for Cutaneous Leishmaniasis","volume":"12","author":"Novais","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1086\/520665","article-title":"Amphotericin B Treatment for Indian Visceral Leishmaniasis: Response to 15 Daily versus Alternate-Day Infusions","volume":"45","author":"Sundar","year":"2007","journal-title":"Clin. Infect. Dis."},{"key":"ref_12","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":"Hamill","year":"2013","journal-title":"Drugs"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"473","DOI":"10.2174\/1389200219666181022163424","article-title":"Anti-leishmanial Nanotherapeutics: A Current Perspective","volume":"20","author":"Shah","year":"2019","journal-title":"Curr. Drug Metab."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"857","DOI":"10.2217\/nnm-2020-0482","article-title":"Nanotechnology approaches for delivery and targeting of Amphotericin B in fungal and parasitic diseases","volume":"16","author":"Jafari","year":"2021","journal-title":"Nanomedicine"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/S0924-8579(99)00133-8","article-title":"A comparison of the activities of three amphotericin B lipid formulations against experimental visceral and cutaneous leishmaniasis","volume":"13","author":"Yardley","year":"2000","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1111\/myc.12283","article-title":"Comparison of nephrotoxicity associated to different lipid formulations of amphotericin B: A real-life study","volume":"58","author":"Falci","year":"2015","journal-title":"Mycoses"},{"key":"ref_17","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_18","doi-asserted-by":"crossref","unstructured":"Faustino, P. (2020). Lipid Systems for the Delivery of Amphotericin B in Antifungal Therapy. Pharmaceutics, 12.","DOI":"10.3390\/pharmaceutics12010029"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"106661","DOI":"10.1016\/j.actatropica.2022.106661","article-title":"Amphotericin B: A drug of choice for Visceral Leishmaniasis","volume":"235","author":"Kumari","year":"2022","journal-title":"Acta Trop."},{"key":"ref_20","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_21","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_22","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_23","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1007\/s40121-020-00382-7","article-title":"Sixty years of Amphotericin B: An overview of the main antifungal agent used to treat invasive fungal infections","volume":"10","author":"Cavassin","year":"2021","journal-title":"Infect. Dis. Ther."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1038\/ja.2010.80","article-title":"A newly identified derivative of amphotericin B: Isolation, structure determination and primary evaluation of the activity and toxicity","volume":"63","author":"Wang","year":"2010","journal-title":"J. Antibiot."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.jconrel.2014.06.007","article-title":"Lipid nanoparticles: Drug localization is substance-specific and achievable load depends on the size and physical state of the particles","volume":"189","author":"Kupetz","year":"2014","journal-title":"J. Control. Release"},{"key":"ref_26","unstructured":"Enna, S.J., and Bylund, D.B. (2008). Amphotericin B. xPharm: The Comprehensive Pharmacology Reference, Elsevier."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1016\/j.colsurfb.2013.01.041","article-title":"Interactions of antileishmanial drugs with monolayers of lipids used in the development of amphotericin B\u2013miltefosine-loaded nanocochleates","volume":"106","author":"Pham","year":"2013","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1016\/j.jconrel.2021.12.019","article-title":"Self-assembling, supramolecular chemistry and pharmacology of amphotericin B: Poly-aggregates, oligomers and monomers","volume":"341","author":"Wallace","year":"2022","journal-title":"J. Control. Release"},{"key":"ref_29","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_30","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0301-4622(96)02241-7","article-title":"Physico-chemical properties of the heat-induced \u2018superaggregates\u2019 of amphotericin B","volume":"66","author":"Gaboriau","year":"1997","journal-title":"Biophys. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.mycmed.2012.10.003","article-title":"New strategy for enhancing the therapeutic index of Fungizone\u00ae","volume":"23","author":"Adida","year":"2013","journal-title":"J. Mycol. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.jpba.2017.08.031","article-title":"Circular dichroism in functional quality evaluation of medicines","volume":"147","author":"Yao","year":"2018","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2518","DOI":"10.1128\/AAC.36.11.2518","article-title":"Effects of aggregation and solvent on the toxicity of amphotericin B to human erythrocytes","volume":"36","author":"Legrand","year":"1992","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/0304-4165(82)90300-2","article-title":"Self-association of some polyene macrolide antibiotics in aqueous media","volume":"719","author":"Mazerski","year":"1982","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2419","DOI":"10.1002\/bip.1977.360161107","article-title":"Structural studies on aqueous and hydroalcoholic solutions of a polyene antibiotic: Amphotericin B","volume":"16","author":"Rinnert","year":"1977","journal-title":"Biopolymers"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1007\/978-1-61779-806-1_3","article-title":"Molecular organization of polyene antibiotic amphotericin B studied by means of fluorescence technique","volume":"875","author":"Gruszecki","year":"2012","journal-title":"Methods Mol. Biol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1511","DOI":"10.1021\/mp300143n","article-title":"Toward understanding of toxic side effects of a polyene antibiotic amphotericin B: Fluorescence spectroscopy reveals widespread formation of the specific supramolecular structures of the drug","volume":"9","author":"Wasko","year":"2012","journal-title":"Mol. Pharm."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"13821","DOI":"10.1021\/jp510245n","article-title":"Self-association of amphotericin B: Spontaneous formation of molecular structures responsible for the toxic side effects of the antibiotic","volume":"118","author":"Starzyk","year":"2014","journal-title":"J. Phys. Chem. B"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1598","DOI":"10.1128\/AAC.44.6.1598-1603.2000","article-title":"Mild heating of amphotericin B-desoxycholate: Effects on ultrastructure, in vitro activity and toxicity, and therapeutic efficacy in severe candidiasis in leukopenic mice","volume":"44","author":"Roovers","year":"2000","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Cuddihy, G., Wasan, E., Di, Y., and Wasan, K. (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_41","doi-asserted-by":"crossref","first-page":"19109","DOI":"10.1038\/srep19109","article-title":"Thermodynamics and kinetics of amphotericin B self-association in aqueous solution characterized in molecular detail","volume":"6","author":"Gruszecki","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1007\/s00249-014-0983-8","article-title":"Recent progress in the study of the interactions of amphotericin B with cholesterol and ergosterol in lipid environments","volume":"43","year":"2014","journal-title":"Eur. Biophys. J."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Carolus, H., Pierson, S., Lagrou, K., and Van Dijck, P. (2020). Amphotericin B and other polyenes\u2014Discovery, clinical use, mode of action and drug resistance. J. Fungi, 6.","DOI":"10.3390\/jof6040321"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"4064628","DOI":"10.1155\/2017\/4064628","article-title":"Increasing the fungicidal action of amphotericin B by inhibiting the nitric oxide-dependent tolerance pathway","volume":"2017","author":"Vriens","year":"2017","journal-title":"Oxid. Med. Cell Longev."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"6627","DOI":"10.1128\/AAC.03570-14","article-title":"The production of reactive oxygen species is a universal action mechanism of amphotericin B against pathogenic yeasts and contributes to the fungicidal effect of this drug","volume":"58","author":"Casas","year":"2014","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2345","DOI":"10.1128\/AAC.41.11.2345","article-title":"Heat-induced superaggregation of amphotericin B reduces its in vitro toxicity: A new way to improve its therapeutic index","volume":"41","author":"Gaboriau","year":"1997","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1038\/nbt.3330","article-title":"Principles of nanoparticle design for overcoming biological barriers to drug delivery","volume":"33","author":"Blanco","year":"2015","journal-title":"Nat. Biotechnol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"16","DOI":"10.2174\/2211738504666160301233754","article-title":"Pharmacokinetics and renal toxicity of monomeric amphotericin B in rats after a multiple dose regimen","volume":"4","author":"Kang","year":"2016","journal-title":"Pharm. Nanotechnol."},{"key":"ref_49","first-page":"141","article-title":"How can micelle systems be rebuilt by a heating process?","volume":"7","author":"Siqueira","year":"2012","journal-title":"Int. J. Nanomed."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1128\/AAC.43.2.390","article-title":"Activity of a heat-induced reformulation of amphotericin B deoxycholate (Fungizone) against Leishmania donovani","volume":"43","author":"Petit","year":"1999","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2186","DOI":"10.1021\/acs.molpharmaceut.0c00313","article-title":"Enhancing safety and efficacy by altering the toxic aggregated state of amphotericin B in lipidic nanoformulations","volume":"17","author":"Das","year":"2020","journal-title":"Mol. Pharm."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"660-IN10","DOI":"10.1016\/S0022-2836(64)80115-7","article-title":"Negative staining of phospholipids and their structural modification by surface-active agents as observed in the electron microscope","volume":"8","author":"Bangham","year":"1964","journal-title":"J. Mol. Biol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2123","DOI":"10.1016\/0024-3205(82)90455-6","article-title":"Stability of small unilamellar liposomes in serum and clearance from the circulation: The effect of the phospholipid and cholesterol components","volume":"30","author":"Senior","year":"1982","journal-title":"Life Sci."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1016\/0304-4165(78)90305-7","article-title":"Effects of bile salts on the structural integrity of liposomes","volume":"543","author":"Richards","year":"1978","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_55","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"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/S0378-5173(03)00158-3","article-title":"Polyethylene glycol-coated liposomes for oral delivery of recombinant human epidermal growth factor","volume":"258","author":"Li","year":"2003","journal-title":"Int. J. Pharm."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"728","DOI":"10.2174\/1567201817666200724170708","article-title":"PEGylated nanoliposomes potentiated oral combination therapy for effective cancer treatment","volume":"17","author":"Singh","year":"2020","journal-title":"Curr. Drug Deliv."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.apsb.2018.06.005","article-title":"Adapting liposomes for oral drug delivery","volume":"9","author":"He","year":"2019","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1473","DOI":"10.1016\/0024-3205(80)90268-4","article-title":"Liposomes\u2014A selective drug delivery system for the topical route of administration. Lotion dosage form","volume":"26","author":"Mezei","year":"1980","journal-title":"Life Sci."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/S0939-6411(03)00021-3","article-title":"Liposomes increase skin penetration of entrapped and non-entrapped hydrophilic substances into human skin: A skin penetration and confocal laser scanning microscopy study","volume":"55","author":"Verma","year":"2003","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1016\/0005-2736(92)90154-E","article-title":"Lipid vesicles penetrate into intact skin owing to the transdermal osmotic gradients and hydration force","volume":"1104","author":"Cevc","year":"1992","journal-title":"Biochim. Biophys. Acta Biomembr. (BBA)-Biomembr."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1016\/j.addr.2003.10.028","article-title":"Lipid vesicles and other colloids as drug carriers on the skin","volume":"56","author":"Cevc","year":"2004","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1093\/jac\/8.5.371","article-title":"Antileishmanial activity of amphotericin and other antifungal agents entrapped in liposomes","volume":"8","author":"New","year":"1981","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1128\/AAC.31.3.421","article-title":"Effect of lipid composition and liposome size on toxicity and in vitro fungicidal activity of liposome-intercalated amphotericin B","volume":"31","author":"Szoka","year":"1987","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"429","DOI":"10.3109\/08982109309150729","article-title":"Development, characterization, efficacy and mode of action of Ambisome, a unilamellar liposomal formulation of amphotericin B","volume":"3","author":"Proffitt","year":"1993","journal-title":"J. Liposome Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/0005-2736(81)90252-2","article-title":"Transfer of the polyene antibiotic amphotericin B between single-walled vesicles of dipalmitoylphosphatidylcholine and egg-yolk phosphatidylcholine","volume":"647","author":"Bolard","year":"1981","journal-title":"Biochim. Biophys. Act-Biomembr."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1668","DOI":"10.1021\/bi00303a014","article-title":"Dissociation kinetics and equilibrium binding properties of polyene antibiotic complexes with phosphatidylcholine\/sterol vesicles","volume":"23","author":"Witzke","year":"1984","journal-title":"Biochemistry"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/S0005-2736(00)00386-2","article-title":"Spectrophotometric analysis of organisation of dipalmitoylphosphatidylcholine bilayers containing the polyene antibiotic amphotericin B","volume":"1511","author":"Koper","year":"2001","journal-title":"Biochim. Biophys. Acta-Biomembr."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/S1011-1344(02)00405-0","article-title":"Dimers of polyene antibiotic amphotericin B detected by means of fluorescence spectroscopy: Molecular organization in solution and in lipid membranes","volume":"69","author":"Gruszecki","year":"2003","journal-title":"J. Photochem. Photobiol. B"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"32780","DOI":"10.1038\/srep32780","article-title":"Molecular organization, localization and orientation of antifungal antibiotic amphotericin B in a single lipid bilayer","volume":"6","author":"Grudzinski","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1093\/jac\/49.suppl_1.21","article-title":"AmBisome: Liposomal formulation, structure, mechanism of action and pre-clinical experience","volume":"49","author":"Proffitt","year":"2002","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1016\/j.ijpharm.2019.04.052","article-title":"Critical process parameters in manufacturing of liposomal formulations of amphotericin B","volume":"565","author":"Rivnay","year":"2019","journal-title":"Int. J. Pharm."},{"key":"ref_73","unstructured":"Proffitt, R.T., Adler-Moore, J., and Chiang, S.-M. (1990). Amphotericin B Liposome Preparation. (WO 59651561999A), US Patent."},{"key":"ref_74","unstructured":"Adler-Moore, J., Gamble, R.C., and Proffitt, R.T. (1991). Treatment of Systemic Fungal Infections with Phospholipid Particles Encapsulating Polyene Antibiotics. (WO US5874104A), US Patent."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.ejpb.2018.11.010","article-title":"Development of a flow-through USP 4 apparatus drug release assay for the evaluation of amphotericin B liposome","volume":"134","author":"Tang","year":"2019","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/j.ejpb.2020.09.008","article-title":"Analytical method development and comparability study for AmBisome\u00ae and generic amphotericin B liposomal products","volume":"157","author":"Liu","year":"2020","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Ramos, G.S., Vallejos, V.M.R., Borges, G.S.M., Almeida, R.M., Alves, I.M., Aguiar, M.M.G., Fernandes, C., Guimar\u00e3es, P.P.G., Fujiwara, R.T., and Loiseau, P.M. (2022). Formulation of amphotericin B in PEGylated liposomes for improved treatment of cutaneous leishmaniasis by parenteral and oral routes. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14050989"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.ijpharm.2011.01.044","article-title":"Characterization of the colloidal properties, in vitro antifungal activity, antileishmanial activity and toxicity in mice of a distigmasterylhemisuccinoyl-glycero-phosphocholine liposome-intercalated amphotericin B","volume":"408","author":"Iman","year":"2011","journal-title":"Int. J. Pharm."},{"key":"ref_79","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_80","doi-asserted-by":"crossref","first-page":"1386","DOI":"10.4049\/jimmunol.181.2.1386","article-title":"Complete cure of experimental visceral leishmaniasis with amphotericin B in stearylamine-bearing cationic liposomes involves down-regulation of IL-10 and favorable t cell responses","volume":"181","author":"Banerjee","year":"2008","journal-title":"J. Immunol."},{"key":"ref_81","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_82","first-page":"105638","article-title":"Nanocarriers Mediated Cutaneous Drug Delivery","volume":"158","author":"Kahraman","year":"2020","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"20780","DOI":"10.3390\/molecules191220780","article-title":"Prodrug strategies for enhancing the percutaneous absorption of drugs","volume":"19","year":"2014","journal-title":"Molecules"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"e202107960","DOI":"10.1002\/anie.202107960","article-title":"Nanocarriers for skin applications: Where do we stand?","volume":"61","author":"Tiwari","year":"2021","journal-title":"Angew. Chem. Int. Ed. Engl."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1021\/acs.molpharmaceut.0c00154","article-title":"Nanodelivery systems for topical management of skin disorders","volume":"18","author":"Cui","year":"2021","journal-title":"Mol. Pharm."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"111748","DOI":"10.1016\/j.colsurfb.2021.111748","article-title":"Skin penetration\/permeation success determinants of nanocarriers: Pursuit of a perfect formulation","volume":"203","author":"Elmowafy","year":"2021","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1039\/D0RA09561C","article-title":"Vesicular systems for dermal and transdermal drug delivery","volume":"11","author":"Richard","year":"2021","journal-title":"RSC Adv."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"13253","DOI":"10.1038\/s41598-018-31693-y","article-title":"Liposomes can both enhance or reduce drugs penetration through the skin","volume":"8","author":"Peralta","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"e00631-18","DOI":"10.1128\/AAC.00631-18","article-title":"Local skin inflammation in cutaneous leishmaniasis as a source of variable pharmacokinetics and therapeutic efficacy of liposomal amphotericin B","volume":"62","author":"Wijnant","year":"2018","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"105988","DOI":"10.1016\/j.actatropica.2021.105988","article-title":"An appraisal of the scientific current situation and new perspectives in the treatment of cutaneous leishmaniasis","volume":"221","author":"Nieva","year":"2021","journal-title":"Acta Trop."},{"key":"ref_91","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":"Carneiro","year":"2012","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Palmer, B., and De Louise, L. (2016). Nanoparticle-enabled transdermal drug delivery systems for enhanced dose control and tissue targeting. Molecules, 21.","DOI":"10.3390\/molecules21121719"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"3271","DOI":"10.2147\/DDDT.S264648","article-title":"Potential of Nanoparticles as permeation enhancers and targeted delivery options for skin: Advantages and disadvantages","volume":"14","author":"Ghasemiyeh","year":"2020","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"L\u00f3pez, L., V\u00e9lez, I., Asela, C., Cruz, C., Alves, F., Robledo, S., and Arana, B. (2018). 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. PLoS Negl. Trop. Dis., 12.","DOI":"10.1371\/journal.pntd.0006653"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"108942","DOI":"10.1016\/j.biopha.2019.108942","article-title":"Niosomal formulation of amphotericin B alone and in combination with glucantime: In vitro and in vivo leishmanicidal effects","volume":"116","author":"Mostafavi","year":"2019","journal-title":"Biomed. Pharmacother."},{"key":"ref_96","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":"Dar","year":"2020","journal-title":"Int. J. Pharm."},{"key":"ref_97","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":"Statts","year":"2020","journal-title":"ACS Infect. Dis."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1208\/s12249-020-01717-w","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":"Riaz","year":"2020","journal-title":"AAPS PharmSciTech"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.ijpharm.2014.07.004","article-title":"New amphotericin B-gamma cyclodextrin formulation for topical use with synergistic activity against diverse fungal species and Leishmania spp","volume":"473","author":"Ruiz","year":"2014","journal-title":"Int. J. Pharm."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"2573","DOI":"10.1021\/acsabm.9b00263","article-title":"Topically applied chitosan-coated poly(isobutylcyanoacrylate) nanoparticles are active against cutaneous leishmaniasis by accelerating lesion healing and reducing the parasitic load","volume":"2","author":"Malli","year":"2019","journal-title":"ACS Appl. Biol. Mater."},{"key":"ref_101","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":"Jaafari","year":"2019","journal-title":"Int. J. Parasitol. Drugs Drug Resist."},{"key":"ref_102","first-page":"269","article-title":"Safety Evaluation of nano-liposomal formulation of amphotericin B (SinaAmpholeish) in animal model as a candidate for treatment of cutaneous leishmaniasis","volume":"12","author":"Eskandari","year":"2018","journal-title":"J. Arthropod. Borne Dis."},{"key":"ref_103","unstructured":"Jaafari, M.R., and Khamesipour, A. (2014). Topical Liposomal Compositions for Delivering Hydrophobic Drugs and Methods Preparing Same. (US20150147382A1), US Patent."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.colsurfb.2015.12.003","article-title":"Topical amphotericin B in ultradeformable liposomes: Formulation, skin penetration study, antifungal and antileishmanial activity in vitro","volume":"139","author":"Perez","year":"2016","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1007\/s13346-021-00910-z","article-title":"Amphotericin B-loaded deformable lipid vesicles for topical treatment of cutaneous leishmaniasis skin lesions","volume":"11","author":"Carvalheiro","year":"2021","journal-title":"Drug Deliv. Transl. Res."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"012027","DOI":"10.1088\/1742-6596\/558\/1\/012027","article-title":"Effect of Amphotericin B antibiotic on the properties of model lipid membrane","volume":"558","author":"Kiryakova","year":"2014","journal-title":"J. Phys. Conf. Ser."},{"key":"ref_107","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":"Khamesipour","year":"2022","journal-title":"East Mediterr. Health J."},{"key":"ref_108","first-page":"197","article-title":"safety evaluation of topical application of nano-liposomal form of amphotericin B (SinaAmpholeish) on healthy volunteers; phase I clinical trial","volume":"14","author":"Eskandari","year":"2019","journal-title":"Iran. J. Parasitol."},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Horev, A., Sagi, O., Zur, E., and Ben-Shimol, S. (2022). Topical liposomal amphotericin B gel treatment for cutaneous leishmaniasis caused by Leishmania major: A double-blind, randomized, placebo-controlled, pilot study. Int. J. Dermatol.","DOI":"10.1111\/ijd.16407"},{"key":"ref_110","first-page":"1","article-title":"Design of amphotericin B oral formulation for antifungal therapy","volume":"24","author":"Liu","year":"2017","journal-title":"Drug Deliv."},{"key":"ref_111","doi-asserted-by":"crossref","unstructured":"Wasan, E., Mandava, T., Crespo-Moran, P., Nagy, A., and Wasan, K.M. (2022). Review of novel oral amphotericin B formulations for the treatment of parasitic infections. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14112316"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1521","DOI":"10.2174\/1381612826666200311130812","article-title":"Development of an oral amphotericin B formulation as an alternative approach to parenteral amphotericin B administration in the treatment of blood-borne fungal infections","volume":"26","author":"Wasan","year":"2020","journal-title":"Curr. Pharm. Des."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1324","DOI":"10.1007\/s11095-009-9841-2","article-title":"Biodegradable nanoparticles improve oral bioavailability of amphotericin B and show reduced nephrotoxicity compared to intravenous Fungizone\u00ae","volume":"26","author":"Italia","year":"2009","journal-title":"Pharm. Res."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1080\/10717544.2016.1228715","article-title":"Oral administration of amphotericin B nanoparticles: Antifungal activity, bioavailability and toxicity in rats","volume":"24","author":"Radwan","year":"2017","journal-title":"Drug Deliv."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"2542","DOI":"10.1021\/mp300320d","article-title":"Gelatin coated hybrid lipid nanoparticles for oral delivery of amphotericin B","volume":"9","author":"Jain","year":"2012","journal-title":"Mol. Pharm."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1166\/jbn.2011.1332","article-title":"AmbiOnp: Solid lipid nanoparticles of amphotericin B for oral administration","volume":"7","author":"Patel","year":"2011","journal-title":"J. Biomed. Nanotechnol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1080\/09205063.2019.1680926","article-title":"Pharmacokinetics and tissue distribution of an orally administered mucoadhesive chitosan-coated amphotericin B-loaded nanostructured lipid carrier (NLC) in rats","volume":"31","author":"Tan","year":"2019","journal-title":"J. Biomater. Sci. Polym. Ed."},{"key":"ref_118","first-page":"327","article-title":"Evaluating the potential of cubosomal nanoparticles for oral delivery of amphotericin B in treating fungal infection","volume":"9","author":"Yang","year":"2014","journal-title":"Int. J. Nanomed."},{"key":"ref_119","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_120","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_121","first-page":"198","article-title":"Amphotericin B cochleates: A vehicle for oral delivery","volume":"5","author":"Perlin","year":"2004","journal-title":"Curr. Opin. Investig. Drugs"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"120688","DOI":"10.1016\/j.ijpharm.2021.120688","article-title":"Cochleate formulations of amphotericin B designed for oral administration using a naturally occurring phospholipid","volume":"603","author":"Nicolas","year":"2021","journal-title":"Int. J. Pharm."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"121985","DOI":"10.1016\/j.ijpharm.2022.121985","article-title":"Pharmacokinetics, biodistribution, and activity of amphotericin B-loaded nanocochleates on the Leishmania donovani murine visceral leishmaniasis model","volume":"624","author":"Pomel","year":"2022","journal-title":"Int. J. Pharm."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"e00838-20","DOI":"10.1128\/AAC.00838-20","article-title":"Phase I EnACT Trial of the safety and tolerability of a novel oral formulation of amphotericin B","volume":"64","author":"Skipper","year":"2020","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"e01450-20","DOI":"10.1128\/AAC.01450-20","article-title":"Safety, tolerability, and pharmacokinetics of a novel oral amphotericin B formulation (ICo-019) following single-dose administration to healthy human subjects: An alternative approach to parenteral amphotericin B administration","volume":"64","author":"Hnik","year":"2020","journal-title":"Antimicrob. Agents Chemother."}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/15\/1\/99\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:53:42Z","timestamp":1760147622000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/15\/1\/99"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,28]]},"references-count":125,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,1]]}},"alternative-id":["pharmaceutics15010099"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics15010099","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,28]]}}}