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The haemolytic activity and cytotoxic and antifungal effects of nanoparticles were assessed in an in vitro model of the blood\u2013brain barrier (BBB). A murine model of disseminated cryptococcosis was used for testing the efficacy of oral treatment with the nanoparticles. In addition, serum biomarkers were measured for toxicity evaluation and the nanoparticle biodistribution was analysed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>P80-functionalized nanoparticles had a mean size of \u223c300 nm, a polydispersity index of \u223c0.4 and zeta potential around \u221250 mV, and they promoted a sustained drug release. Both nanoparticles were effective in decreasing the infection process across the BBB model and reduced drug cytotoxicity and haemolysis. In in vivo cryptococcosis, the oral treatment with two doses of P80 nanoparticles reduced the fungal burden in the brain and lungs, while the non-functionalized nanoparticles reduced fungal amount only in the lungs, and the free miltefosine was not effective. In addition, the P80-functionalization improved the nanoparticle distribution in several organs, especially in the brain. Finally, treatment with nanoparticles did not cause any toxicity in animals.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These results support the potential use of P80-functionalized alginate nanoparticles as miltefosine carriers for non-toxic and effective alternative oral treatment, enabling BBB translocation and reduction of fungal infection in the brain.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jac\/dkad053","type":"journal-article","created":{"date-parts":[[2023,2,16]],"date-time":"2023-02-16T17:17:13Z","timestamp":1676567833000},"page":"1092-1101","source":"Crossref","is-referenced-by-count":17,"title":["Oral delivery of brain-targeted miltefosine-loaded alginate nanoparticles functionalized with polysorbate 80 for the treatment of cryptococcal meningitis"],"prefix":"10.1093","volume":"78","author":[{"given":"Cristina C","family":"Spadari","sequence":"first","affiliation":[{"name":"Institute of Biomedical Sciences, University of S\u00e3o Paulo , S\u00e3o Paulo, SP ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dylan M","family":"Lanser","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, University of California , Davis, CA ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcelo V","family":"Ara\u00fajo","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Sciences, University of S\u00e3o Paulo , S\u00e3o Paulo, SP ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel F F","family":"De Jesus","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Sciences, University of S\u00e3o Paulo , S\u00e3o Paulo, SP ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luciana 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