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Glucan particles (GPs), derived from Saccharomyces cerevisiae yeast, possess unique biomedical properties. Nevertheless, it is imperative that a comprehensive risk assessment is conducted during pre-clinical development. GPs are primarily constituted of a naturally occurring polymer known as \u03b2-glucan. This study characterized GPs, focusing on physicochemical attributes, biocompatibility, and immunomodulatory potential. Methods: GPs were characterized for size, morphology, surface charge, and protein encapsulation efficiency using dynamic light scattering (DLS), electron microscopy, and encapsulation assays. Biocompatibility was assessed through cytotoxicity assays (MTT), hemolysis tests, and measurement of reactive oxygen (ROS) and nitric oxide (NO) production in immune cells. Immunomodulatory potential was evaluated by cytokine and chemokine secretion analysis in peripheral blood mononuclear cells (PBMCs) and monocyte-derived dendritic cells (moDCs) and through in vivo immunization studies in a murine model, focusing on cellular immune responses. Results: GPs demonstrated stable physicochemical properties and efficient protein encapsulation, highlighting their suitability as vaccine delivery systems. They exhibited biocompatibility by not inducing cytotoxicity, hemolysis, or excessive ROS and NO production. In PBMCs, GPs stimulated cytokine secretion, suggesting their adjuvant potential. GPs were efficiently internalized by monocytes and led to specific chemokine secretion in stimulated moDCs. In a murine model, GPs induced distinctive cellular immune responses, including TNF-\u03b1 and IFN-\u03b3 production and effector memory T cell activation. Conclusions: These findings emphasize GPs\u2019 biocompatibility and immunomodulatory effects, highlighting their potential in immunotherapy and vaccine development, particularly for targeting infectious agents like hepatitis B virus.<\/jats:p>","DOI":"10.3390\/pharmaceutics17081032","type":"journal-article","created":{"date-parts":[[2025,8,8]],"date-time":"2025-08-08T13:20:09Z","timestamp":1754659209000},"page":"1032","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Yeast-Derived Glucan Particles: Biocompatibility, Efficacy, and Immunomodulatory Potential as Adjuvants and Delivery Systems"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2414-8945","authenticated-orcid":false,"given":"Jo\u00e3o","family":"Pan\u00e3o-Costa","sequence":"first","affiliation":[{"name":"CNC-UC\u2014Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal"},{"name":"CIBB\u2014Center for Innovative Biomedicine and Biotechnology, University of Coimbra, 3004-504 Coimbra, Portugal"},{"name":"Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariana","family":"Cola\u00e7o","sequence":"additional","affiliation":[{"name":"CNC-UC\u2014Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal"},{"name":"CIBB\u2014Center for Innovative Biomedicine and Biotechnology, University of Coimbra, 3004-504 Coimbra, Portugal"},{"name":"Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4014-9072","authenticated-orcid":false,"given":"Sandra","family":"Jesus","sequence":"additional","affiliation":[{"name":"CNC-UC\u2014Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal"},{"name":"CIBB\u2014Center for Innovative Biomedicine and Biotechnology, University of Coimbra, 3004-504 Coimbra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filipa","family":"Lebre","sequence":"additional","affiliation":[{"name":"Nanosafety Group, International Iberian Nanotechnology Laboratory, 4715-330 Braga, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9846-6754","authenticated-orcid":false,"given":"Maria T.","family":"Cruz","sequence":"additional","affiliation":[{"name":"CNC-UC\u2014Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal"},{"name":"CIBB\u2014Center for Innovative Biomedicine and Biotechnology, University of Coimbra, 3004-504 Coimbra, Portugal"},{"name":"Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1132-7992","authenticated-orcid":false,"given":"Ernesto","family":"Alfaro-Moreno","sequence":"additional","affiliation":[{"name":"Nanosafety Group, International Iberian Nanotechnology Laboratory, 4715-330 Braga, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2215-5121","authenticated-orcid":false,"given":"Olga","family":"Borges","sequence":"additional","affiliation":[{"name":"CNC-UC\u2014Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal"},{"name":"CIBB\u2014Center for Innovative Biomedicine and Biotechnology, University of Coimbra, 3004-504 Coimbra, Portugal"},{"name":"Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2761","DOI":"10.4161\/hv.29589","article-title":"Applications of nanomaterials as vaccine adjuvants","volume":"10","author":"Zhu","year":"2014","journal-title":"Hum. 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