{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T19:16:45Z","timestamp":1770146205904,"version":"3.49.0"},"reference-count":90,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2020,9,9]],"date-time":"2020-09-09T00:00:00Z","timestamp":1599609600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>The control of leishmaniases, a complex parasitic disease caused by the protozoan parasite Leishmania, requires continuous innovation at the therapeutic and vaccination levels. Chitosan is a biocompatible polymer administrable via different routes and possessing numerous qualities to be used in the antileishmanial strategies. This review presents recent progress in chitosan research for antileishmanial applications. First data on the mechanism of action of chitosan revealed an optimal in vitro intrinsic activity at acidic pH, high-molecular-weight chitosan being the most efficient form, with an uptake by pinocytosis and an accumulation in the parasitophorous vacuole of Leishmania-infected macrophages. In addition, the immunomodulatory effect of chitosan is an added value both for the treatment of leishmaniasis and the development of innovative vaccines. The advances in chitosan chemistry allows pharmacomodulation on amine groups opening various opportunities for new polymers of different size, and physico-chemical properties adapted to the chosen routes of administration. Different formulations have been studied in experimental leishmaniasis models to cure visceral and cutaneous leishmaniasis, and chitosan can act as a booster through drug combinations with classical drugs, such as amphotericin B. The various architectural possibilities given by chitosan chemistry and pharmaceutical technology pave the way for promising further developments.<\/jats:p>","DOI":"10.3390\/molecules25184123","type":"journal-article","created":{"date-parts":[[2020,9,10]],"date-time":"2020-09-10T22:58:01Z","timestamp":1599778681000},"page":"4123","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Chitosan Contribution to Therapeutic and Vaccinal Approaches for the Control of Leishmaniasis"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8542-6793","authenticated-orcid":false,"given":"Philippe M.","family":"Loiseau","sequence":"first","affiliation":[{"name":"Antiparasite Chemotherapy, CNRS, BioCIS, Universit\u00e9 Paris-Saclay, 92290 Ch\u00e2tenay-Malabry, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9294-3967","authenticated-orcid":false,"given":"S\u00e9bastien","family":"Pomel","sequence":"additional","affiliation":[{"name":"Antiparasite Chemotherapy, CNRS, BioCIS, Universit\u00e9 Paris-Saclay, 92290 Ch\u00e2tenay-Malabry, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simon L.","family":"Croft","sequence":"additional","affiliation":[{"name":"Faculty of Infectious and Tropical Diseases, London School of Hygiene &amp; Tropical Medicine, London WC1E 7HT, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,9,9]]},"reference":[{"key":"ref_1","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_2","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1007\/s00436-019-06575-5","article-title":"Environmental and socioeconomic risk factors associated with visceral and cutaneous leishmaniasis: A systematic review","volume":"119","author":"Valero","year":"2020","journal-title":"Parasitol. Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1478","DOI":"10.1111\/j.1469-0691.2011.03630.x","article-title":"Leishmaniasis chemotherapy: Challenges and opportunities","volume":"17","author":"Croft","year":"2011","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1177\/1087057114555846","article-title":"High-throughput screening platform for natural product-based drug discovery against three neglected tropical diseases: Human African trypanosomiasis, leishmaniasis, and Chagas disease","volume":"20","author":"Annang","year":"2015","journal-title":"J. Biomol. Screen."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"186","DOI":"10.3389\/fcimb.2019.00186","article-title":"GDP-Mannose Pyrophosphorylase: A biologically validated target for drug development against leishmaniasis","volume":"9","author":"Pomel","year":"2019","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"El Hajj, R., Bou Youness, H., Lachaud, L., Bastien, P., Masquefa, C., Bonnet, P.A., El Hajj, H., and Khalifeh, I. (2018). EAPB0503: An imiquimod analog with potent in vitro activity against cutaneous leishmaniasis caused by Leishmania major and Leishmania tropica. PLoS Negl. Trop. Dis., 12.","DOI":"10.1371\/journal.pntd.0006854"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Intakhan, N., Chanmol, W., Somboon, P., Bates, M.D., Yardley, V., Bates, P.A., and Jariyapan, N. (2020). Antileishmanial activity and synergistic effects of amphotericin B deoxycholate with allicin and andrographolide against Leishmania martiniquensis in vitro. Pathogens, 9.","DOI":"10.3390\/pathogens9010049"},{"key":"ref_8","first-page":"1","article-title":"Use of liposomal nanoformulations in antileishmania therapy: Challenges and perspectives","volume":"31","author":"Echeverry","year":"2020","journal-title":"J. Liposome Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.actatropica.2011.02.007","article-title":"Systematic review of the adverse effects of cutaneous leishmaniasis treatment in the New World","volume":"118","author":"Oliveira","year":"2011","journal-title":"Acta Trop."},{"key":"ref_10","first-page":"S154","article-title":"Chitin\/chitosan and its derivatives: Fundamental problems and practical approaches","volume":"85","author":"Varlamov","year":"2020","journal-title":"Biochemistry"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1016\/j.ijbiomac.2020.03.148","article-title":"Advances and applications of chitosan-based nanomaterials as oral delivery carriers: A review","volume":"154","author":"Lang","year":"2020","journal-title":"Int. Biol. Macromol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"7623","DOI":"10.1038\/s41598-018-26043-x","article-title":"Carvacrol and linalool co-loaded in b-cyclodextrin-grafted chitosan nanoparticles as sustainable biopesticide aiming pest control","volume":"8","author":"Campos","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1082","DOI":"10.1016\/j.ijbiomac.2020.03.031","article-title":"Entrapment of enzyme aggregates in chitosan beads for aroma release in white wines","volume":"154","author":"Tavernini","year":"2020","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Hu, Z., Zhang, D.Y., Lu, S.T., Li, P.W., and Li, S.D. (2018). Chitosan-based composite materials for prospective hemostatic applications. Mar. Drugs, 16.","DOI":"10.3390\/md16080273"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1854","DOI":"10.3390\/ijms14011854","article-title":"Quaternized chitosan as an antimicrobial agent: Antimicrobial activity, mechanism of action and biomedical applications in orthopedics","volume":"14","author":"Tan","year":"2013","journal-title":"Int. J. Mol. Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ijbiomac.2005.12.009","article-title":"Antifungal efficacy of chitosan and its thiourea derivatives upon the growth of some sugarbeet pathogens","volume":"38","author":"Eweis","year":"2006","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1007\/978-3-319-92486-1_20","article-title":"Glycans with antiviral activity from marine organisms","volume":"65","author":"Grice","year":"2018","journal-title":"Results Probl. Cell Differ."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1016\/j.ijbiomac.2018.05.205","article-title":"Modified chitosan-based bioactive material for antimicrobial application: Synthesis and characterization","volume":"117","author":"Braz","year":"2018","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/j.ijbiomac.2013.06.025","article-title":"Enzymatic degradation and bioactivity evaluation of C-6 oxidized chitosan","volume":"60","author":"Pierre","year":"2013","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.biomaterials.2018.08.054","article-title":"Immunomodulatory properties of chitosan polymers","volume":"184","author":"Moran","year":"2018","journal-title":"Biomaterials"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"195","DOI":"10.15171\/apb.2019.023","article-title":"Current advances in chitosan nanoparticles based drug delivery and targeting","volume":"9","author":"Garg","year":"2019","journal-title":"Adv. Pharm. Bull."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1016\/j.ejpb.2012.04.007","article-title":"Chitosan-based delivery systems","volume":"81","year":"2012","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2117","DOI":"10.3390\/md8072117","article-title":"Neuroprotective properties of chitosan and its derivatives","volume":"8","author":"Pangestuti","year":"2010","journal-title":"Mar. Drugs"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Wang, W., Meng, Q., Li, Q., Liu, J., Zhou, M., Jin, Z., and Zhao, K. (2020). Chitosan derivatives and their application in biomedicine. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21020487"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"199","DOI":"10.3109\/10717544.2013.801533","article-title":"Biomaterials as novel penetration enhancers for transdermal and dermal drug delivery systems","volume":"20","author":"Chen","year":"2013","journal-title":"Drug Deliv."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1016\/j.ijbiomac.2019.01.072","article-title":"Chitosan based-asymmetric membranes for wound healing: A review","volume":"127","author":"Miguel","year":"2019","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"111","DOI":"10.4103\/0972-9062.242557","article-title":"Potent antileishmanial activity of chitosan against Iranian strain of Leishmania major (MRHO\/IR\/75\/ER): In vitro and in vivo assay","volume":"55","author":"Esboei","year":"2018","journal-title":"J. Vector Borne Dis."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e01772-19","DOI":"10.1128\/AAC.01772-19","article-title":"Activity of chitosan and its derivatives against Leishmania major and Leishmania mexicana in vitro","volume":"64","author":"Riezk","year":"2020","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"115839","DOI":"10.1016\/j.carbpol.2020.115839","article-title":"Wound healing and antimicrobial effect of active secondary metabolites in chitosan-based wound dressings: A review","volume":"233","author":"Moeini","year":"2020","journal-title":"Carbohydr. Polym."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1080\/17425247.2019.1634051","article-title":"Hyaluronic acid and chitosan-based nanosystems: A new dressing generation for wound care","volume":"16","author":"Vigani","year":"2019","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.1111\/iwj.12797","article-title":"Chitin and chitosan: Biopolymers for wound management","volume":"14","author":"Singh","year":"2017","journal-title":"Int. Wound J."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"4617","DOI":"10.1007\/s00436-015-4707-5","article-title":"Potential application of nanochitosan film as a therapeutic agent against cutaneous leishmaniasis caused by L. major","volume":"114","author":"Bahrami","year":"2015","journal-title":"Parasitol. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"609","DOI":"10.4103\/ijdvl.IJDVL_189_18","article-title":"Chitosan-based biocompatible dressing for treatment of recalcitrant lesions of cutaneous leishmaniasis: A pilot clinical study","volume":"85","author":"Abdollahimajd","year":"2019","journal-title":"Indian J. Dermatol. Venereol. Leprol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3129","DOI":"10.2217\/nnm-2018-0063","article-title":"Novel nano-sized chitosan amphotericin B formulation with considerable improvement against Leishmania major","volume":"13","author":"Ardestani","year":"2018","journal-title":"Nanomedicine"},{"key":"ref_35","first-page":"5341","article-title":"An optimized nanoparticle delivery system based on chitosan and chondroitin sulfate molecules reduces the toxicity of amphotericin B and is effective in treating tegumentary leishmaniasis","volume":"9","author":"Ribeiro","year":"2014","journal-title":"Int. J. Nanomed."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1309","DOI":"10.1007\/s12010-014-1084-y","article-title":"Chitosan-assisted immunotherapy for intervention of experimental leishmaniasis via amphotericin B-loaded solid lipid nanoparticles","volume":"174","author":"Jain","year":"2014","journal-title":"Appl. Biochem. Biotechnol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1727","DOI":"10.1007\/s11095-014-1571-4","article-title":"Self assembled ionically sodium alginate cross-linked amphotericin B encapsulated glycol chitosan stearate nanoparticles: Applicability in better chemotherapy and non-toxic delivery in visceral leishmaniasis","volume":"32","author":"Gupta","year":"2015","journal-title":"Pharm. Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"99","DOI":"10.2217\/nnm-2016-0325","article-title":"Development of mannose-achored thiolated amphotericin B nanocarriers for treatment of visceral leishmaniasis","volume":"12","author":"Shahnaz","year":"2017","journal-title":"Nanomedicine"},{"key":"ref_39","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_40","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_41","doi-asserted-by":"crossref","first-page":"3452","DOI":"10.1021\/bm0604000","article-title":"Carbohydrate-based micelle clusters which enchance hydrophobic drug bioavailability by up to 1 order of magnitude","volume":"7","author":"Qu","year":"2006","journal-title":"Biomacromolecules"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1021\/mp200469a","article-title":"Enchanced oral absorption of hydrophobic and hydrophilic drugs using quaternary ammonium palmitoyl glycol chitosan nanoparticles","volume":"9","author":"Siew","year":"2012","journal-title":"Mol. Pharm."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.colsurfb.2015.08.037","article-title":"Development of 4-sulfated N-acetyl galactosamine anchored chitosan nanoparticles: A dual strategy for effective management of leishmaniasis","volume":"136","author":"Tripathi","year":"2015","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"7593","DOI":"10.2147\/IJN.S220410","article-title":"Comparative analysis between four model nanoformulations of amphotericin B-chitosan, amphotericin B-dendrimer, betulinic acid-chitosan and betulinic acid-dendrimer for treatment of Leishmania major: Real-time PCR assay plus","volume":"14","author":"Khamesipour","year":"2019","journal-title":"Int. J. Nanomed."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"105072","DOI":"10.1016\/j.actatropica.2019.105072","article-title":"Paromomycin-loaded mannosylated chitosan nanoparticles: Synthesis, characterization and targeted drug delivery against leishmaniasis","volume":"197","author":"Esfandiari","year":"2019","journal-title":"Acta Trop."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"387","DOI":"10.2217\/nnm-2018-0038","article-title":"Mannosylated thiolated paromomycin-loaded PLGA nanoparticles for the oral therapy of visceral leishmaniasis","volume":"14","author":"Afzal","year":"2019","journal-title":"Nanomedicine"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"25","DOI":"10.2217\/nnm-2017-0255","article-title":"Mannosylated thiolated polyethyleneimine nanoparticles or the enhanced efficacy of antimonial drugs against leishmaniasis","volume":"13","author":"Sarwar","year":"2018","journal-title":"Nanomedicine"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.1007\/s00436-008-0901-z","article-title":"In vitro evaluation of the effectiveness and cytotoxicity of meglumine antimoniate microspheres produced by spray drying against Leishmania infantum","volume":"102","author":"Pujals","year":"2008","journal-title":"Parasitol. Res."},{"key":"ref_49","first-page":"618","article-title":"New World tegumentar leishmaniasis: Chemotherapeutic activity of rifampicin in humans and experimental murine model","volume":"43","author":"Schubach","year":"1995","journal-title":"Pathol. Biol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1111\/j.1365-4362.1987.tb04578.x","article-title":"Efficacy of rifampicin and isoniazid in cutaneous leishmaniasis","volume":"26","author":"Livshin","year":"1987","journal-title":"Int. J. Dermatol."},{"key":"ref_51","first-page":"161","article-title":"A double blind, randomised placebo controlled trial of rifampicin with omeprazole in the treatment of human cutaneous leishmaniasis","volume":"43","author":"Kochar","year":"2006","journal-title":"J. Vector Borne Dis."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"183","DOI":"10.2217\/nnm-2019-0320","article-title":"Rifampicin-loaded nanotransferosomal gel for treatment of cutaneous leishmaniasis: Passive targeting via topical route","volume":"15","author":"Rabia","year":"2020","journal-title":"Nanomedicine"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1002\/ardp.200900319","article-title":"Curcumin in cancer chemoprevention: Molecular targets, pharmacokinetics, bioavailability, and clinical trials","volume":"343","author":"Shehzad","year":"2010","journal-title":"Arch. Pharm."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"117","DOI":"10.15420\/ecr.2019.17.2","article-title":"Anti-inflammatory action of curcumin and its use in the treatment of lifestyle-related diseases","volume":"14","author":"Shimizu","year":"2019","journal-title":"Eur. Cardiol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2738","DOI":"10.3748\/wjg.v22.i9.2736","article-title":"Curcumin as a potential therapeutic candidate for Helicobacter pylori associated disease","volume":"22","author":"Sarkar","year":"2016","journal-title":"World J. Gastroenterol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2116","DOI":"10.2174\/13895575113136660101","article-title":"Chalcone and curcumin derivatives: A way ahead for malarial treatment","volume":"13","author":"Kumar","year":"2013","journal-title":"Mini Rev. Med. Chem."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1007\/s10495-008-0224-7","article-title":"Reactive oxygen species and imbalance of calcium homeostasis contributes to curcumin induced programmed cell death in Leishmania donovani","volume":"13","author":"Das","year":"2008","journal-title":"Apoptosis"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1038\/s41420-019-0178-2","article-title":"A novel hydrolase with a pro-death activity from the protozoan parasite Leishmania major","volume":"5","author":"Basmaciyan","year":"2019","journal-title":"Cell Death Discov."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.ijbiomac.2017.12.143","article-title":"Mannose-conjugated curcumin-chitosan nanoparticles: Efficacy and toxicity assessments against Leishmania donovani","volume":"111","author":"Chaubey","year":"2018","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"42","DOI":"10.2174\/1874848100902010042","article-title":"Preclinical and clinical studies of lapachol and beta-lapachone","volume":"2","year":"2009","journal-title":"Open Nat. Prod. J."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1016\/j.ejmech.2013.02.038","article-title":"Potent naphtoquinones against antimony-sensitive and -resistant Leishmania parasites: Synthesis of a novel \u03b1- and nor-\u03b1-lapachone-based 1,2,3-triazoles by copper-catalyzed azide-alkyne cycloaddition","volume":"63","author":"Guimaraes","year":"2013","journal-title":"Eur. J. Med. Chem."},{"key":"ref_62","first-page":"905","article-title":"\u03b2-lapachone accelerates the recovery of burn-wound skin","volume":"26","author":"Fu","year":"2011","journal-title":"Histol. Histopathol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"C931","DOI":"10.1152\/ajpcell.00266.2008","article-title":"In vitro and in vivo wound healing-promoting activities of beta-lapachone","volume":"295","author":"Kung","year":"2008","journal-title":"Am. J. Physiol. Cell. Physiol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"2003","DOI":"10.1016\/j.nano.2015.07.011","article-title":"Assessement of \u03b2-lapachone loaded in lecithin-chitosan nanoparticles for the topical treatment of cutaneous leishmaniasis in L. major infected BALB\/c mice","volume":"11","author":"Moreno","year":"2015","journal-title":"Nanomedicine"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"657","DOI":"10.2174\/0929867053202214","article-title":"Betulinic acid and its derivatives: A review on their biological properties","volume":"12","author":"Yogeeswari","year":"2005","journal-title":"Curr. Med. Chem."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.exppara.2016.04.007","article-title":"Antiparasitic evaluation of betulinic acid derivatives reveals effective and selective anti-Trypanosoma cruzi inhibitors","volume":"166","author":"Meira","year":"2016","journal-title":"Exp. Parasitol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1016\/j.phymed.2009.08.002","article-title":"Antiprotozoal activity of Betulinic acid derivatives","volume":"17","year":"2010","journal-title":"Phytomedicine"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1124\/mol.111.072785","article-title":"Novel betulin derivatives as antileishmanial agents with mode of action targeting type IB DNA topoisomerase","volume":"80","author":"Chowdhury","year":"2011","journal-title":"Mol. Pharmacol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"11759","DOI":"10.1038\/s41598-018-30103-7","article-title":"Novel nanosized chitosan-betulinic acic against resistant Leishmania major and girts clinical observation of such parasite in kidney","volume":"8","author":"Khamesipour","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Bilbao-Ramos, P., Serrano, D.R., Ruiz Saldana, H.K., Torrado, J.J., Bolas-Fernandez, F., and Dea-Avuela, M.A. (2020). Evaluating the potential of ursolic acid as bioproduct for cutaneous and visceral leishmaniasis. Molecules, 25.","DOI":"10.3390\/molecules25061394"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1016\/j.ijbiomac.2017.04.098","article-title":"Oral delivery of ursolic acid-loaded nanostructured lipid carrier coated with chitosanoligosaccharides: Development, characterization, in vitro and in vivo assessment for the therapy of leishmaniasis","volume":"102","author":"Das","year":"2017","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.niox.2019.09.007","article-title":"Nitric oxide-loaded chitosan nanoparticles as an innovative antileishmanial platform","volume":"93","author":"Cabral","year":"2019","journal-title":"Nitric Oxide"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1007\/s11095-017-2117-3","article-title":"Supramolecular chitosan micro-platelets synergistically enchance anti-Candida albicans activity of amphotericin B using an immunocompetent murine model","volume":"34","author":"Grisin","year":"2017","journal-title":"Pharm. Res."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1016\/j.ijpharm.2017.01.048","article-title":"Cyclodextrin-mediated self-associating chitosan micro-platelets acts as a drug booster against Candida glabrata mucosal infection in immunocompetent mice","volume":"519","author":"Grisin","year":"2017","journal-title":"Int. J. Pharm."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.jddst.2018.12.031","article-title":"Combination of amphotericin B and chitosan platelets for the treatment of experimental cutaneous leishmaniasis: Histological and immunohistochemical examinations","volume":"50","author":"Malli","year":"2019","journal-title":"J. Drug Deliv. Sci. Technol."},{"key":"ref_76","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. Biomater."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.ijpharm.2015.06.001","article-title":"Cell line-dependent cytotoxicity of poly(isobutylcyanoacrylate) nanoparticles coated with chitosan and thiolated chitosan: Insights from cultured human epithelial Hela, Caco2\/TC7 and HT29\/MTX cells","volume":"491","author":"Pradines","year":"2015","journal-title":"Int. J. Pharm."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1016\/j.ijbiomac.2017.07.076","article-title":"Hexadecylphosphocholine (Miltefosine) stabilized chitosan modified ampholipospheres as prototype co-delivery vehicle for enhanced killing of L. donovani","volume":"105","author":"Tripathi","year":"2017","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/j.ejps.2014.06.010","article-title":"Topical treatment of L. major infected BALB\/c mice with a novel diselenide chitosan hydrogel formulation","volume":"62","author":"Schwartz","year":"2014","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1016\/j.ijbiomac.2017.08.177","article-title":"Chitosan-titanium dioxide-glucantime nanoassemblies effects on promastigote and amastigote of Leishmania major","volume":"107","author":"Varshosaz","year":"2018","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.parint.2015.10.007","article-title":"Immunotherapeutic effects of chitin in comparison with chitosan against Leishmania major infection","volume":"65","author":"Hoseini","year":"2016","journal-title":"Parasitol. Int."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1220","DOI":"10.1016\/j.ijbiomac.2017.07.161","article-title":"Chitosan coated PluronicF127 micelles for effective delivery of Amphotericin B in experimental visceral leishmaniasis","volume":"105","author":"Singh","year":"2017","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1714","DOI":"10.1128\/AAC.01984-12","article-title":"Immunoadjuvant chemotherapy of visceral leishmaniasis in hamsters using amphotericin B-encapsulated nanoemulsion template-based chitosan nanocapsules","volume":"57","author":"Asthana","year":"2013","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"2992","DOI":"10.1016\/j.vaccine.2015.12.071","article-title":"Status of vaccine research and development of vaccines for leishmaniasis","volume":"34","author":"Gillespie","year":"2016","journal-title":"Vaccine"},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Osman, M., Mistry, A., Keding, A., Gabe, R., Cook, E., Forrester, S., Wiggins, R., Di Marco, S., Colloca, S., and Siani, L. (2017). A Third Generation Vaccine for Human Visceral Leishmaniasis and Post Kala Azar Dermal Leishmaniasis: First-in-human Trial of ChAd63-KH. PLoS Negl. Trop. Dis., 11.","DOI":"10.1371\/journal.pntd.0005527"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1016\/j.immuni.2016.03.002","article-title":"Chitosan: An adjuvant with an unanticipated STING","volume":"44","author":"Riteau","year":"2016","journal-title":"Immunity"},{"key":"ref_87","first-page":"281","article-title":"Chitosan nanoparticles loaded with whole and soluble Leishmania antigens, and evaluation of their immunogenicity in a mouse model of leishmaniasis","volume":"15","author":"Hojatizade","year":"2018","journal-title":"Iran J. Immunol."},{"key":"ref_88","first-page":"835","article-title":"Nanovaccine for leishmaniasis: Preparation of chitosan nanoparticles containing Leishmania superoxide dismutase and evaluation of its immunogenicity in BALB\/c mice","volume":"6","author":"Shokri","year":"2011","journal-title":"Int. J. Nanomed."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1111\/j.1462-5822.2008.01132.x","article-title":"Leishmania chitinase facilitates colonization of sandfly vectors and enhances transmission to mice","volume":"10","author":"Rogers","year":"2008","journal-title":"Cell Microbiol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"243","DOI":"10.3389\/fbioe.2019.00243","article-title":"Enzymatic modifications of chitin, chitosan and chito-oligosaccarides","volume":"7","author":"Kaczmarek","year":"2019","journal-title":"Front. Bioeng. Biotechnol."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/25\/18\/4123\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:08:25Z","timestamp":1760177305000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/25\/18\/4123"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,9]]},"references-count":90,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2020,9]]}},"alternative-id":["molecules25184123"],"URL":"https:\/\/doi.org\/10.3390\/molecules25184123","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9,9]]}}}