Dual-loaded chitosan-based nanoparticles: a novel approach for treating polymicrobial osteomyelitis

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.

Description

The 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.

Keywords

Biofilm infections Chitosan Drug delivery system Minocycline Minocycline hydrochloride Mixed osteomyelitis Polysaccharide nanoparticles Poloxamer Voriconazole FCT_UIDB/05608/2020 FCT_UIDP/05608/2020

URI

http://hdl.handle.net/10400.21/21735

Citation

Zegre 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.