{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T15:28:29Z","timestamp":1785770909156,"version":"3.56.0"},"reference-count":65,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2024,3,25]],"date-time":"2024-03-25T00:00:00Z","timestamp":1711324800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004484","name":"Tehran University of Medical Sciences and Health Services","doi-asserted-by":"publisher","award":["99-2-211-49861"],"award-info":[{"award-number":["99-2-211-49861"]}],"id":[{"id":"10.13039\/501100004484","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p><jats:italic>Acanthamoeba<\/jats:italic> keratitis (AK) is a corneal sight-threatening infection caused by the free-living amoebae of the genus <jats:italic>Acanthamoeba<\/jats:italic>. Early and appropriate treatment significantly impacts visual outcomes. Mucoadhesive polymers such as chitosan are a potential strategy to prolong the residence time and bioavailability of the encapsulated drugs in the cornea. Regarding the recent administration of miltefosine (MF) for treating resistant AK, in the present study, we synthesized miltefosine-loaded chitosan nanoparticles (MF-CS-NPs) and evaluated them against <jats:italic>Acanthamoeba<\/jats:italic>.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methodology\/Principal findings<\/jats:title>\n<jats:p>Chitosan nanoparticles (CNPs) were prepared using the ionic gelation method with negatively charged tripolyphosphate (TPP). The zeta-potential (ZP) and the particle size of MF-CS-NPs were 21.8\u00b13.2 mV and 46.61\u00b118.16 nm, respectively. The release profile of MF-CS-NPs indicated linearity with sustained drug release. The cytotoxicity of MF-CS-NPs on the <jats:italic>Vero<\/jats:italic> cell line was 2.67 and 1.64 times lower than free MF at 24 and 48 hours. This formulation exhibited no hemolytic activity <jats:italic>in vitro<\/jats:italic> and ocular irritation in rabbit eyes. The IC<jats:sub>50<\/jats:sub> of MF-CS-NPs showed a significant reduction by 2.06 and 1.69-fold in trophozoites at 24 and 48 hours compared to free MF. Also, the MF-CS-NPs IC<jats:sub>50<\/jats:sub> in the cysts form was slightly decreased by 1.26 and 1.21-fold at 24 and 48 hours compared to free MF.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>The MF-CS-NPs were more effective against the trophozoites and cysts than free MF. The nano-chitosan formulation was more effective on trophozoites than the cysts form. MF-CS-NPs reduced toxicity and improved the amoebicidal effect of MF. Nano-chitosan could be an ideal carrier that decreases the cytotoxicity of miltefosine. Further analysis in animal settings is needed to evaluate this nano-formulation for clinical ocular drug delivery.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pntd.0011976","type":"journal-article","created":{"date-parts":[[2024,3,25]],"date-time":"2024-03-25T17:35:14Z","timestamp":1711388114000},"page":"e0011976","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":21,"title":["Chitosan nanoparticles improve the effectivity of miltefosine against Acanthamoeba"],"prefix":"10.1371","volume":"18","author":[{"given":"Alireza","family":"Latifi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fariba","family":"Esmaeili","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehdi","family":"Mohebali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Setayesh","family":"Yasami-Khiabani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mostafa","family":"Rezaeian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad","family":"Soleimani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8634-5584","authenticated-orcid":true,"given":"Elham","family":"Kazemirad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amir","family":"Amani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,3,25]]},"reference":[{"issue":"1","key":"pntd.0011976.ref001","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.joco.2018.09.008","article-title":"Acanthamoeba keratitis\u2013Clinical signs, differential diagnosis and treatment.","volume":"31","author":"N Szentm\u00e1ry","year":"2019","journal-title":"J Curr Ophthalmol"},{"issue":"6","key":"pntd.0011976.ref002","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1016\/j.jiph.2023.03.020","article-title":"The global epidemiology and clinical diagnosis of Acanthamoeba keratitis.","volume":"16","author":"Y Zhang","year":"2023","journal-title":"J Infect Public Health"},{"issue":"1","key":"pntd.0011976.ref003","doi-asserted-by":"crossref","first-page":"e000476","DOI":"10.1136\/bmjophth-2020-000476","article-title":"Personal hygiene risk factors for contact lens-related microbial keratitis","volume":"5","author":"A Stellwagen","year":"2020","journal-title":"BMJ Open Ophthalmol"},{"key":"pntd.0011976.ref004","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1051\/parasite\/2015010","article-title":"An update on Acanthamoeba keratitis: diagnosis, pathogenesis and treatment.","volume":"22","author":"J Lorenzo-Morales","year":"2015","journal-title":"Parasite."},{"issue":"1","key":"pntd.0011976.ref005","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1186\/s13104-017-2666-x","article-title":"Development and validation of a real-time PCR assay for the detection of clinical acanthamoebae","volume":"10","author":"N Karsenti","year":"2017","journal-title":"BMC Res Notes"},{"issue":"3","key":"pntd.0011976.ref006","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.clae.2017.12.017","article-title":"Acanthamoeba in the eye, can the parasite hide even more? Latest developments on the disease.","volume":"41","author":"MM Juarez","year":"2018","journal-title":"Cont Lens Anterior Eye."},{"issue":"5","key":"pntd.0011976.ref007","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1016\/j.ajo.2007.01.015","article-title":"Therapeutic keratoplasty for advanced suppurative keratitis","volume":"143","author":"S-E Ti","year":"2007","journal-title":"Am J Ophthalmol"},{"issue":"4","key":"pntd.0011976.ref008","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1136\/bjophthalmol-2019-314485","article-title":"Acanthamoeba keratitis therapy: time to cure and visual outcome analysis for different antiamoebic therapies in 227 cases","volume":"104","author":"V Papa","year":"2020","journal-title":"Br J Ophthalmol"},{"issue":"11","key":"pntd.0011976.ref009","doi-asserted-by":"crossref","first-page":"6441","DOI":"10.1128\/AAC.00686-16","article-title":"The development of drugs against Acanthamoeba infections","volume":"60","author":"R Siddiqui","year":"2016","journal-title":"Antimicrob Agents Chemother"},{"issue":"1","key":"pntd.0011976.ref010","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13071-019-3323-0","article-title":"Use of miltefosine to treat canine visceral leishmaniasis caused by Leishmania infantum in Brazil.","volume":"12","author":"F dos Santos Nogueira","year":"2019","journal-title":"Parasit Vectors"},{"key":"pntd.0011976.ref011","doi-asserted-by":"crossref","first-page":"107009","DOI":"10.1016\/j.actatropica.2023.107009","article-title":"Comparing cytotoxicity and efficacy of miltefosine and standard antimicrobial agents against Acanthamoeba trophozoites and cyst forms: An in vitro study","volume":"247","author":"A Latifi","year":"2023","journal-title":"Acta Trop"},{"key":"pntd.0011976.ref012","doi-asserted-by":"crossref","first-page":"271","DOI":"10.2147\/OPTO.S235679","article-title":"Common ophthalmic preservatives in soft contact lens care products: benefits, complications, and a comparison to non-preserved solutions.","author":"CS Bradley","year":"2021","journal-title":"Clin Optom (Auckl)."},{"key":"pntd.0011976.ref013","first-page":"100555","article-title":"Oral miltefosine for refractory Acanthamoeba keratitis","volume":"16","author":"KE Hirabayashi","year":"2019","journal-title":"American Am J Ophthalmol Case Rep"},{"key":"pntd.0011976.ref014","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1007\/978-3-319-29346-2_26","article-title":"Challenges in ocular pharmacokinetics and drug delivery.","author":"JS Macwan","year":"2016","journal-title":"Nano-biomaterials for ophthalmic drug delivery"},{"issue":"46","key":"pntd.0011976.ref015","doi-asserted-by":"crossref","first-page":"27835","DOI":"10.1039\/D0RA04971A","volume":"10","author":"S Gorantla","year":"2020","journal-title":"RSC Adv"},{"issue":"7","key":"pntd.0011976.ref016","doi-asserted-by":"crossref","first-page":"1403","DOI":"10.3390\/nano10071403","article-title":"Polymeric nanoparticles for drug delivery: Recent developments and future prospects.","volume":"10","author":"B Begines","year":"2020","journal-title":"Nanomaterials (Basel)."},{"issue":"3","key":"pntd.0011976.ref017","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.3390\/md13031133","article-title":"Chitin and chitosan preparation from marine sources. Structure, properties and applications.","volume":"13","author":"I Younes","year":"2015","journal-title":"Mar Drugs"},{"issue":"7","key":"pntd.0011976.ref018","first-page":"2626","article-title":"Chitin, chitosan and their pharmacological activities: a review","volume":"9","author":"K Tripathi","year":"2018","journal-title":"Int J Pharm Sci Res"},{"key":"pntd.0011976.ref019","doi-asserted-by":"crossref","first-page":"1278","DOI":"10.3889\/oamjms.2022.10005","article-title":"Primaquine-chitosan Nanoparticle Improves Drug Delivery to Liver Tissue in Rats.","volume":"10","author":"M Louisa","year":"2022","journal-title":"Open Access Maced. J. Med. Sci"},{"issue":"17","key":"pntd.0011976.ref020","doi-asserted-by":"crossref","DOI":"10.3390\/molecules25174002","article-title":"Activity of Amphotericin B-Loaded Chitosan Nanoparticles against Experimental Cutaneous Leishmaniasis.","volume":"25","author":"A Riezk","year":"2020","journal-title":"Molecules"},{"issue":"12","key":"pntd.0011976.ref021","doi-asserted-by":"crossref","first-page":"370","DOI":"10.3390\/md15120370","article-title":"Chitosan nanoparticles as a mucoadhesive drug delivery system for ocular administration.","volume":"15","author":"MM Silva","year":"2017","journal-title":"Mar Drugs"},{"issue":"7","key":"pntd.0011976.ref022","doi-asserted-by":"crossref","first-page":"1519","DOI":"10.3390\/polym12071519","article-title":"Chitosan and its derivatives for ocular delivery formulations: Recent advances and developments.","volume":"12","author":"A Zamboulis","year":"2020","journal-title":"Polymers (Basel)."},{"issue":"3","key":"pntd.0011976.ref023","first-page":"51","article-title":"Chitosan nanoparticles: a promising system for drug delivery.","volume":"11","author":"W. Tiyaboonchai","year":"2013","journal-title":"J. nat. sci."},{"issue":"5","key":"pntd.0011976.ref024","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1039\/c2an15641e","article-title":"Characterization and identification of suspected counterfeit miltefosine capsules.","volume":"137","author":"TP Dorlo","year":"2012","journal-title":"Analyst."},{"issue":"1","key":"pntd.0011976.ref025","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1038\/s41598-021-04427-w","article-title":"Characterization of cisplatin-loaded chitosan nanoparticles and rituximab-linked surfaces as target-specific injectable nano-formulations for combating cancer","volume":"12","author":"MH Sultan","year":"2022","journal-title":"Sci Rep"},{"issue":"1\u201324","key":"pntd.0011976.ref026","volume":"4","author":"I. Guideline","year":"2003","journal-title":"Stability testing of new drug substances and products. Q1A (R2), current step"},{"key":"pntd.0011976.ref027","doi-asserted-by":"crossref","first-page":"100","DOI":"10.3389\/fbioe.2020.00100","article-title":"Chitosan nanoparticles: shedding light on immunotoxicity and hemocompatibility.","volume":"8","author":"S Jesus","year":"2020","journal-title":"Front Bioeng Biotechnol"},{"issue":"2","key":"pntd.0011976.ref028","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/j.ejop.2012.11.004","article-title":"A systematic analysis of Acanthamoeba genotype frequency correlated with source and pathogenicity: T4 is confirmed as a pathogen-rich genotype.","volume":"49","author":"SK Maciver","year":"2013","journal-title":"Eur J protistol."},{"issue":"3","key":"pntd.0011976.ref029","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1007\/s00436-020-06997-6","article-title":"Management of refractory Acanthamoeba keratitis, two cases","volume":"120","author":"M Soleimani","year":"2021","journal-title":"Parasitol Res"},{"issue":"11","key":"pntd.0011976.ref030","doi-asserted-by":"crossref","first-page":"3932","DOI":"10.1128\/JCM.38.11.3932-3936.2000","article-title":"Discrimination between clinically relevant and nonrelevant Acanthamoeba strains isolated from contact lens-wearing keratitis patients in Austria","volume":"38","author":"J Walochnik","year":"2000","journal-title":"J Clin Microbiol"},{"issue":"3","key":"pntd.0011976.ref031","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1128\/AAC.46.3.695-701.2002","article-title":"Cytotoxic activities of alkylphosphocholines against clinical isolates of Acanthamoeba spp","volume":"46","author":"J Walochnik","year":"2002","journal-title":"Antimicrob Agents Chemother"},{"issue":"1","key":"pntd.0011976.ref032","doi-asserted-by":"crossref","first-page":"8053","DOI":"10.1038\/s41598-021-87381-x","article-title":"Anti-Acanthamoeba synergistic effect of chlorhexidine and Garcinia mangostana extract or \u03b1-mangostin against Acanthamoeba triangularis trophozoite and cyst forms.","volume":"11","author":"S Sangkanu","year":"2021","journal-title":"Sci Rep"},{"issue":"2","key":"pntd.0011976.ref033","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1093\/jac\/40.2.227","article-title":"Effects of biocides on Acanthamoeba castellanii as measured by flow cytometry and plaque assay","volume":"40","author":"W Khunkitti","year":"1997","journal-title":"J Antimicrob Chemother"},{"key":"pntd.0011976.ref034","author":"Development Cooperation OfE","year":"2002","journal-title":"Test No. 405: Acute Eye Irritation"},{"issue":"9","key":"pntd.0011976.ref035","doi-asserted-by":"crossref","first-page":"1208","DOI":"10.3390\/nano9091208","article-title":"Poly (cyclohexene phthalate) nanoparticles for controlled dasatinib delivery in breast cancer therapy.","volume":"9","author":"E Niza","year":"2019","journal-title":"Nanomaterials (Basel)"},{"issue":"5","key":"pntd.0011976.ref036","doi-asserted-by":"crossref","DOI":"10.3390\/jcm10050942","article-title":"Challenges in Acanthamoeba Keratitis: A Review.","volume":"10","author":"G Varacalli","year":"2021","journal-title":"J Clin Med."},{"issue":"1","key":"pntd.0011976.ref037","first-page":"25","article-title":"Optimization and development of insulin nanoparticles by new thiolated chitosan derivative with ionic gelation method using a model-based methodology","volume":"2","author":"Z Mahdizadeh Barzoki","year":"2019","journal-title":"J Food Bioprocess Eng"},{"key":"pntd.0011976.ref038","doi-asserted-by":"crossref","first-page":"4911","DOI":"10.2147\/IJN.S375570","article-title":"An update on novel ocular nanosystems with possible benefits in the treatment of corneal neovascularization.","author":"C Zhang","year":"2022","journal-title":"Int J Nanomedicine"},{"key":"pntd.0011976.ref039","first-page":"190","author":"Qiaoli Yi","year":"2023"},{"issue":"16","key":"pntd.0011976.ref040","doi-asserted-by":"crossref","DOI":"10.3390\/nano12162808","article-title":"Ciprofloxacin-Loaded Silver Nanoparticles as Potent Nano-Antibiotics against Resistant Pathogenic Bacteria.","volume":"12","author":"DR Ibraheem","year":"2022","journal-title":"Nanomaterials (Basel)."},{"issue":"11","key":"pntd.0011976.ref041","doi-asserted-by":"crossref","first-page":"1451","DOI":"10.1211\/0022357022476","article-title":"The potential of chitosan in ocular drug delivery","volume":"55","author":"MJ Alonso","year":"2003","journal-title":"J Pharm Pharmacol"},{"issue":"5","key":"pntd.0011976.ref042","doi-asserted-by":"crossref","first-page":"593","DOI":"10.3109\/10837450.2013.813542","article-title":"Preparation and characterization of self-assembled chitosan nanoparticles for the sustained delivery of streptokinase: an in vivo study","volume":"19","author":"SMS Modaresi","year":"2014","journal-title":"Pharm Dev Technol"},{"issue":"1","key":"pntd.0011976.ref043","doi-asserted-by":"crossref","first-page":"e08674","DOI":"10.1016\/j.heliyon.2021.e08674","article-title":"Drug release study of the chitosan-based nanoparticles.","volume":"8","author":"Y Herdiana","year":"2022","journal-title":"Heliyon"},{"issue":"3","key":"pntd.0011976.ref044","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/j.yexmp.2008.12.004","article-title":"Nanoparticle-based targeted drug delivery","volume":"86","author":"R Singh","year":"2009","journal-title":"Exp Mol Pathol"},{"issue":"2","key":"pntd.0011976.ref045","doi-asserted-by":"crossref","DOI":"10.17795\/jjnpp-23082","article-title":"Preparation and in vitro evaluation of chitosan nanoparticles containing diclofenac using the ion-gelation method.","volume":"10","author":"M Kouchak","year":"2015","journal-title":"Jundishapur J Nat Pharm Prod"},{"issue":"13","key":"pntd.0011976.ref046","doi-asserted-by":"crossref","first-page":"7432","DOI":"10.1021\/acsomega.0c00111","article-title":"Developing biodegradable nanoparticles loaded with mometasone furoate for potential nasal drug delivery.","volume":"5","author":"J Far","year":"2020","journal-title":"ACS omega."},{"key":"pntd.0011976.ref047","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.ijbiomac.2019.11.157","article-title":"Preparation of PEG-grafted chitosan\/streptokinase nanoparticles to improve biological half-life and reduce immunogenicity of the enzyme","volume":"143","author":"H Baharifar","year":"2020","journal-title":"Int J Biol Macromol"},{"key":"pntd.0011976.ref048","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1016\/j.ijbiomac.2015.01.056","article-title":"Synthesis and characterization of chitosan derivatives with dual-antibacterial functional groups","volume":"75","author":"Z Li","year":"2015","journal-title":"Int J Biol Macromol"},{"key":"pntd.0011976.ref049","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.etap.2018.05.017","article-title":"Lithium entrapped chitosan nanoparticles to reduce toxicity and increase cellular uptake of lithium","volume":"61","author":"S. Narayan","year":"2018","journal-title":"Environ Toxicol Pharmacol"},{"issue":"Pt 1","key":"pntd.0011976.ref050","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":"P Tripathi","year":"2017","journal-title":"Int J Biol Macromol"},{"key":"pntd.0011976.ref051","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":"FV Cabral","year":"2019","journal-title":"Nitric oxide"},{"issue":"19","key":"pntd.0011976.ref052","doi-asserted-by":"crossref","DOI":"10.3390\/ma15196521","article-title":"Chitosan Nanoparticles: A Versatile Platform for Biomedical Applications.","volume":"15","author":"SM Bashir","year":"2022","journal-title":"Materials (Basel)."},{"issue":"2","key":"pntd.0011976.ref053","doi-asserted-by":"crossref","first-page":"472","DOI":"10.3390\/pharmaceutics15020472","article-title":"Potential Oral Anticancer Therapeutic Agents of Hexahydrocurcumin-Encapsulated Chitosan Nanoparticles against MDA-MB-231 Breast Cancer Cells","volume":"15","author":"FN Sorasitthiyanukarn","year":"2023","journal-title":"Pharmaceutics"},{"issue":"3","key":"pntd.0011976.ref054","first-page":"e13698","article-title":"Miltefosine: A Miracle Drug for Meningoencephalitis Caused by Free-Living Amoebas.","volume":"13","author":"A Alli","year":"2021","journal-title":"Cureus"},{"key":"pntd.0011976.ref055","doi-asserted-by":"crossref","first-page":"6383","DOI":"10.2147\/IJN.S142060","article-title":"Intracellular disposition of chitosan nanoparticles in macrophages: intracellular uptake, exocytosis, and intercellular transport.","volume":"12","author":"LQ Jiang","year":"2017","journal-title":"Int J Nanomedicine"},{"issue":"4","key":"pntd.0011976.ref056","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":"V Jain","year":"2014","journal-title":"Appl Biochem Biotechnol"},{"key":"pntd.0011976.ref057","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.colsurfb.2013.05.018","article-title":"pH-responsive drug delivery of chitosan nanoparticles as Tamoxifen carriers for effective anti-tumor activity in breast cancer cells","volume":"111","author":"R Vivek","year":"2013","journal-title":"Colloids Surf B Biointerfaces"},{"key":"pntd.0011976.ref058","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13071-015-0642-7","article-title":"Cellulose degradation: a therapeutic strategy in the improved treatment of Acanthamoeba infections.","volume":"8","author":"S Lakhundi","year":"2015","journal-title":"Parasit Vectors"},{"key":"pntd.0011976.ref059","doi-asserted-by":"crossref","first-page":"108008","DOI":"10.1016\/j.exppara.2020.108008","article-title":"Nanoparticles based therapeutic efficacy against Acanthamoeba: Updates and future prospect","volume":"218","author":"G Sharma","year":"2020","journal-title":"Exp Parasitol"},{"issue":"2","key":"pntd.0011976.ref060","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1007\/s12639-020-01204-w","article-title":"Investigation of the in vitro cysticidal activity of miltefosine against Acanthamoeba spp.","volume":"44","author":"M Chao","year":"2020","journal-title":"J Parasit Dis."},{"key":"pntd.0011976.ref061","doi-asserted-by":"crossref","first-page":"101692","DOI":"10.1016\/j.mtcomm.2020.101692","article-title":"Cellular uptake and retention of nanoparticles: Insights on particle properties and interaction with cellular components","volume":"25","author":"R Augustine","year":"2020","journal-title":"Mater. Today Commun"},{"issue":"10","key":"pntd.0011976.ref062","doi-asserted-by":"crossref","DOI":"10.3390\/pharmaceutics13101686","article-title":"Chitosan Nanoparticles at the Biological Interface: Implications for Drug Delivery.","volume":"13","author":"N Aibani","year":"2021","journal-title":"Pharmaceutics"},{"key":"pntd.0011976.ref063","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1016\/j.ijbiomac.2016.05.016","article-title":"The potential application of hyaluronic acid coated chitosan nanoparticles in ocular delivery of dexamethasone","volume":"89","author":"MA Kalam","year":"2016","journal-title":"Int J Biol Macromol"},{"key":"pntd.0011976.ref064","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1016\/j.ijbiomac.2018.04.122","article-title":"Chitosan coated PLGA nanoparticles amplify the ocular hypotensive effect of forskolin: Statistical design, characterization and in vivo studies","volume":"116","author":"N Khan","year":"2018","journal-title":"Int J Biol Macromol"},{"key":"pntd.0011976.ref065","doi-asserted-by":"crossref","first-page":"7861","DOI":"10.2147\/IJN.S269004","article-title":"Clarithromycin-loaded ocular chitosan nanoparticle: formulation, optimization, characterization, ocular irritation, and antimicrobial activity.","author":"M Bin-Jumah","year":"2020","journal-title":"Int J Nanomedicine."}],"container-title":["PLOS Neglected Tropical Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pntd.0011976","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,25]],"date-time":"2024-03-25T17:36:05Z","timestamp":1711388165000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pntd.0011976"}},"subtitle":[],"editor":[{"given":"Aiman","family":"Abu Ammar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2024,3,25]]},"references-count":65,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2024,3,25]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pntd.0011976","relation":{},"ISSN":["1935-2735"],"issn-type":[{"value":"1935-2735","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,25]]}}}