The use of chitosan nanoparticles (CH-NPs) loaded with antibiotics as irrigants in endodontics offers a unique combination, demonstrating effective antibacterial activity and low toxicity. Therefore, the aim of this study was to develop chitosan nanoparticles loaded with metronidazole, ciprofloxacin, and minocycline for use as endodontic irrigants to improve antibacterial activity against Enterococcus faecalis and to evaluate their cytotoxicity in human dental pulp stem cells (hDPSCs). Methods: The CH-NPs loaded with antibiotics were synthesized and analyzed using Fourier Transform Infrared Spectroscopy (FTIR) and Ultraviolet-visible spectroscopy (UV-Vis). Agar diffusion and microdilution assays were performed to determine the minimum inhibitory concentration (MIC), and a cytotoxicity assay was conducted to establish the median cytotoxic dose. Results: Peaks corresponding to the functional groups of the chitosan-antibiotic complex’s chemical structure were identified. A one-way ANOVA (p ≤ 0.05) with Tukey’s post hoc test was used to analyze the antibacterial effect. CH-NPs-ciprofloxacin showed the greatest antibacterial activity against E. faecalis in both agar diffusion and microdilution assays. CH-NPs-metronidazole demonstrated lower cytotoxicity against hDPSCs. CH-NPs-minocycline showed superior antibacterial effects compared to plain chitosan in microdilution assays, although they exhibited greater cytotoxicity. Conclusions: The ongoing search for an irrigating solution with effective antibacterial properties and low cytotoxicity could transform traditional techniques. However, this field is still developing and underexplored. It is essential to reevaluate decisions about irrigation solutions, as evidence on the use of chitosan nanoparticles with antibiotics is limited. This study provides valuable data for endodontics and is a crucial step for future research.

Orthodontic adhesives can accumulate biofilm, which may lead to long-term white-spot lesions; however, incorporating poly (lactic-co-glycolic acid) (PLGA) nanoparticles could improve their anticariogenic properties. Objective: To develop PLGA nanoparticles containing antiseptic agents for orthodontic adhesives, improve antibacterial activity against Streptococcus mutans, and assess cytotoxicity in gingival fibroblasts. Methods: PLGA nanoparticles with chlorhexidine and chitosan were synthesized and characterized using FTIR, SEM, and UV-Vis spectroscopy. Antibacterial activity was evaluated by agar diffusion and microdilution assays, and cytotoxicity and microhardness were also assessed. Results: PLGA-NPs showed moderate antibacterial effects, with inhibition rates from 74.25% to 54.05% in agar diffusion and reduced activity in microdilution (CC50: 3.75 µg/mL in adhesive, 15 µg/mL free). PLGA-NPs-CHx exhibited stronger antibacterial activity, with inhibition ranging from 89.38% to 73.75% and a CC50 of 0.93 µg/mL in both forms. PLGA-NPs-CH also showed significant inhibition (83.11% to 69.39%) and a CC50 of 1.87 µg/mL in adhesive and 7.5 µg/mL free. Vickers microhardness values were similar across groups: 74.67 HV for adhesive only, 74.11 HV for adhesive with PLGA-NPs, 74.22 HV for PLGA-NPs-CH-Adh, and 74 HV for PLGA-NPs-CHx-Adh. Conclusions: Incorporating PLGA nanoparticles functionalized with antiseptic agents into orthodontic adhesives shows promising antibacterial potential and may benefit orthodontic practice.