Enterococcus faecalis plays the key role in endodontic infections and is responsible for the formation of biofilm on dentin, which causes a resistance against periradicular lesions treatment, consequently the aim of this study is to use nanoparticles entrapping anibacterial agents coated with chitosan that in authors previous study showed a successful in vitro biofilm inhibition, additionally incorporated in thermoresponsive gel.to benefit nanoparticles` small size, and the positive charge of their surfaces that binds with the negatively charged surface of bacterial cell causing its destruction, in addition to the sustained release pattern of the drug based nanoparticles in gel. Therefore, Ciprofloxacin hydrochloride (CIP) encapsulated in PLGA nanoparticles coated with chitosan (CIP-CS-PLGA-NPs), in addition to free CIP, were incorporated in Pluronic® 407/188 to form thermosensitive gels (F1) and (F2), respectively. The thermosensitive gels were tested with regards to rheology, gelling temperature and the release pattern of the drug. A clinical study of the efficacy of F1 and F2 as antibacterial treatments was conducted on patients followed by a comparative studies against CIP and Ca(OH)₂ pastes in terms of biofilm inhibition assay and total bacterial reduction count and percent.The results revealed that F1 and F2 exhibited gelation temperature of 36.9 ± 0.3 °C and 36.0 ± 0.4 °C, viscosity was 15,000 ± 360.6 and 7023.3 ± 296.8 cP respectively. The cumulative release of F1 and F2 after 72 h was 50.03% ± 0.7345 and 77.98% ± 3.122 respectively. F1 was the most efficient treatment against recurrent E.faecalis infection in endodontics that was evident by the highest total bacterial reduction count and percent and biofilm inhibition percent that were recorded in the group treated with F1followed by the group treated with F2. Nanocarriers succeeded in carrying the drug deeply in the root canal and sustaining its effect to abolish the obstinate E. faecalis recurrent infection and its biofilm formation.

Background: Effective management of bone defects remains a major clinical challenge, driving continuous efforts to develop bioactive, localized delivery systems that support bone regeneration. Gold nanoparticles (AuNPs) have gained attention in regenerative medicine for their capacity to modulate cellular activity. Yet, their application in functional delivery systems for bone repair is still limited. Chitosan (CS), a naturally derived biopolymer, exhibits notable osteoinductive properties, particularly when used to modify nanoparticulate carriers. Objectives: In this study, AuNPs and chitosan-coated gold nanoparticles (CS-AuNPs) were formulated, characterized, and incorporated into gel preparations to evaluate their physicochemical properties and therapeutic potential in a rat tibial bone defect model. Methods: AuNPs were synthesized and either left uncoated or coated with CS to enhance biological activity. Both formulations were examined for particle size, zeta potential, X-ray diffraction, and Fourier-transform infrared spectroscopy (FTIR). The resulting nanoparticles were integrated into gel bases, which were assessed for gel strength, swelling index, viscosity, and pH. The in vivo study involved surgically induced bone defects in the tibias of albino rats treated with either formulation. Healing outcomes were assessed via histological analysis, quantification of newly formed bone, immunohistochemical staining, radiographic imaging, and measurement of bone-related markers using RT-qPCR. Results: The CS-AuNP gel formulation demonstrated significantly improved bone regeneration compared to the uncoated counterpart, as evidenced by histological findings, increased bone volume in radiographs, stronger immunohistochemical expression of the VEGF angiogenic protein marker, and increased genetic expression of osteogenic markers. Conclusions: Incorporating CS-AuNPs into gel formulations offers a promising approach for enhancing bone healing. The superior performance of the CS-coated system highlights its potential as a promising localized therapy for managing bone defects.

Background: Oral squamous cell carcinoma (OSCC) remains challenging due to the limited efficacy and toxicity of current therapies. This study investigates the anticancer potential of Captopril–Montmorillonite (CP–MMT) (nanoclay-based delivery system), a drug-repurposing approach in which Captopril is incorporated within MMT nanoclay layered silicate carrier. To our knowledge, this formulation has not been previously investigated in OSCC cell lines, demonstrating enhanced anticancer efficacy. The aim of the work was to compare the anticancer effects of CP–MMT formulation with free Captopril in OSCC cell lines, focusing on cytotoxicity, apoptosis, cell-cycle arrest, oxidative stress, and key molecular markers. Methods: CP–MMT nanoclay-based formulation was synthesised via solution-intercalation, characterised (particle size, polydispersity, and zeta potential), and biologically evaluated in laryngeal (HEP-2) and tongue cancer (HN-9) cells using cytotoxicity (MTT), apoptosis (Annexin V/PI), cell-cycle profiling, oxidative stress assays, including Total Antioxidant Capacity (TAC), Glutathione (GSH), and gene expression analysis for molecular markers (BAX, BCL-2, P53, CASPASE-3, Ki-67, and IL-6). Results: CP–MMT formulation significantly increased apoptosis, induced robust G2 and S-phase arrest, increased pro-apoptotic gene expression (BAX: 3.8-fold, P53: 2.9-fold, CASPASE-3: 2.7-fold), and downregulated anti-apoptotic and proliferative markers (BCL-2: 0.6-fold, Ki-67: 0.3-fold, and IL-6: 0.3-fold ; p < 0.05). CP–MMT formulation reduced cell viability, with IC₅₀ values of 30 µM in HN-9, ~ 40 µM in HEP-2, ~ 115 µM in OEC, compared to the minimal effects of free Captopril. Oxidative stress was increased, as shown by reduced TAC (0.2 mM) and GSH (0.2 mg/dL) levels in CP–MMT-treated HN-9 cells. Conclusions: The CP–MMT formulation showed enhanced anticancer activity compared to free Captopril in vitro, with effects on apoptosis, cell proliferation, and cellular redox balance. These findings are limited to in vitro conditions and should be interpreted cautiously. Further validation in in vivo and advanced 3D tumour models is required.