Zegre, MiguelBarros, J.David, A. B.Fialho, L.Ferraz, M. P.Monteiro, F. J.Caetano, Liliana AranhaGonçalves, L.Bettencourt, A.2025-04-022025-04-022025-04Zegre M, Barros J, David AB, Fialho L, Ferraz MP, Caetano LA, et al. Dual-loaded chitosan-based nanoparticles: a novel approach for treating polymicrobial osteomyelitis. Int J Pharm. 2025;674:125480.0378-5173http://hdl.handle.net/10400.21/21735The authors thank the Fundação para a Ciência e Tecnologia (FCT), Portugal for the financial support of the projects: UIDB/04138/2020 and UIDP/04138/2020 (iMed.Ulisboa); UIDB/05608/2020 and UIDP/05608/2020 (H&TRC). L. Gonçalves, Principal Researcher grant (CEECIND/03143/2017); J. Barros, Junior Researcher Grant (2022.05157.CEECIND/CP1735 /CT0011) and thanks to project Agenda “Health from Portugal - HfPT” [C630926586-00465198], co-financed by the Recovery and Resilience Plan (RRP) and by the European funds NextGeneration EU (https://recuperarportugal.gov.pt/), through the Incentive System “Agendas for Business Innovation”. The Graphical Abstract was created with Biorender.com.Developing innovative approaches to target osteomyelitis caused by polymicrobial infections remains a significant therapeutic challenge. In this study, monodispersed chitosan nanoparticles co-loaded with antibacterial (minocycline) and antifungal (voriconazole) agents were successfully prepared. Minocycline presented higher encapsulation efficiency as compared to voriconazole. Thermostability analysis suggested interactions between the co-loaded drugs within the dual-delivery system, potentially limiting voriconazole release. The dual-loaded chitosan nanoparticles exhibited significant in vitro anti-biofilm activity, achieving up to a 90% reduction in polymicrobial biofilms of S. aureus and C. albicans. Additionally, the nanoparticles showed cytocompatibility with a human osteoblast cell line. These findings highlight the potential of this dual-delivery chitosan-based nanoparticle system to address a critical gap in osteomyelitis treatment by targeting both bacterial and fungal pathogens.engBiofilm infectionsChitosanDrug delivery systemMinocyclineMinocycline hydrochlorideMixed osteomyelitisPolysaccharide nanoparticlesPoloxamerVoriconazoleFCT_UIDB/05608/2020FCT_UIDP/05608/2020journal article10.1016/j.ijpharm.2025.125480