{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T09:48:46Z","timestamp":1792316926831,"version":"4.4.0"},"reference-count":50,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,8,20]],"date-time":"2021-08-20T00:00:00Z","timestamp":1629417600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004396","name":"Thailand Research Fund","doi-asserted-by":"publisher","award":["PHD59I0019"],"award-info":[{"award-number":["PHD59I0019"]}],"id":[{"id":"10.13039\/501100004396","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>In this study, we describe a nano-carrier system for propolis that is able to cross an <jats:italic>in vitro<\/jats:italic> model of the blood-brain barrier (BBB) and effectively reduce the virulence of <jats:italic>Cryptococcus neoformans<\/jats:italic> in animal models. Antimicrobial properties of propolis have been widely studied. However, propolis applications are limited by its low water solubility and poor bioavailability. Therefore, we recently formulated novel poly (n-butyl cyanoacrylate) nanoparticles (PBCA-NP) containing propolis. PBCA-NP are biocompatible, biodegradable and have been shown to effectively cross the BBB using apolipoprotein E (ApoE) as a ligand. Prepared nanoparticles were characterized for particle size, zeta potential, propolis entrapment efficiency and <jats:italic>in vitro<\/jats:italic> release. Additionally, the PBCA-NP were functionalized with polysorbate 80, which then specifically adsorbs ApoE. Using an <jats:italic>in vitro<\/jats:italic> BBB model of human brain microvascular endothelial cells hCMEC\/D3, it was shown that fluorescence labelled ApoE-functionalized PBCA-NP were internalized by the cells and translocated across the cell monolayer. Propolis-loaded PBCA-NP had <jats:italic>in vitro<\/jats:italic>, antifungal activity against <jats:italic>C. neoformans<\/jats:italic>, which causes meningitis. To utilize the invertebrate model, <jats:italic>Galleria mellonella<\/jats:italic> larvae were infected with <jats:italic>C. neoformans<\/jats:italic> and treated with propolis-loaded PBCA-NP. The larvae exhibited normal behavior in toxicity testing, and treatment with propolis-loaded PBCA-NP increased survival in the <jats:italic>C. neoformans<\/jats:italic>-infected larvae group. In addition, following cryptococcal infection and then 7\u00a0days of treatment, the tissue fungal burden of mice treated with propolis-loaded PBCA-NP was significantly lower than control groups. Therefore, our ApoE-functionalized propolis-loaded PBCA-NP can be deemed as a potential targeted nanoparticle in the therapeutic treatment of cerebral cryptococcosis.<\/jats:p>","DOI":"10.3389\/fphar.2021.723727","type":"journal-article","created":{"date-parts":[[2021,8,20]],"date-time":"2021-08-20T11:03:26Z","timestamp":1629457406000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":33,"title":["Targeted Propolis-Loaded Poly (Butyl) Cyanoacrylate Nanoparticles: An Alternative Drug Delivery Tool for the Treatment of Cryptococcal Meningitis"],"prefix":"10.3389","volume":"12","author":[{"given":"Patcharin","family":"Thammasit","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chayada Sitthidet","family":"Tharinjaroen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingmanee","family":"Tragoolpua","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Volker","family":"Rickerts","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Radostina","family":"Georgieva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans","family":"B\u00e4umler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khajornsak","family":"Tragoolpua","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,8,20]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1016\/s0378-5173(02)00076-5","article-title":"Investigation of Polymeric Nanoparticles as Carriers of Enalaprilat for Oral Administration","volume":"239","author":"Ahlin","year":"2002","journal-title":"Int. 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