Peritumoral Microgel Reservoir for Long-Term Light-Controlled Triple-Synergistic Treatment of Osteosarcoma with Single Ultra-Low Dose.

Local minimally invasive injection of anticancer therapies is a compelling approach to maximize the utilization of drugs and reduce the systemic adverse drug effects. However, the clinical translation is still hampered by many challenges such as short residence time of therapeutic agents and the difficulty in achieving multi-modulation combination therapy. Herein, mesoporous silica-coated gold nanorods (AuNR@SiO2 ) core-shell nanoparticles are fabricated to facilitate drug loading while rendering them photothermally responsive. Subsequently, AuNR@SiO2 is anchored into a monodisperse photocrosslinkable gelatin (GelMA) microgel through one-step microfluidic technology. Chemotherapeutic drug doxorubicin (DOX) is loaded into AuNR@SiO2 and 5,6-dimethylxanthenone-4-acetic acid (DMXAA) is loaded in the microgel layer. The osteosarcoma targeting ligand alendronate is conjugated to AuNR@SiO2 to improve the tumor targeting. The microgel greatly improves the injectability since they can be dispersed in buffer and the injectability and degradability are adjustable by microfluidics during the fabrication. The drug release can, in turn, be modulated by multi-round light-trigger. Importantly, a single super low drug dose (1 mg kg-1 DOX with 5 mg kg-1 DMXAA) with peritumoral injection generates long-term therapeutic effect and significantly inhibited tumor growth in osteosarcoma bearing mice. Therefore, this nanocomposite@microgel system can act as a peritumoral reservoir for long-term effective osteosarcoma treatment.

Mesoporous silica nanoparticles facilitating the dissolution of poorly soluble drugs in orodispersible films.

Orodispersible films (ODF) are immediately dissolving/disintegrating intraoral dosage forms, presented as substitutes of conventional tablets or capsules to ease problems associated with swallowing. Efforts have been made to be able to exploit ODFs as dosage forms for poorly soluble drugs. In the last two decades, mesoporous silica nanoparticles (MSNs) have been extensively used in drug delivery applications to overcome solubility problems of drugs. The tunable features of MSNs make them suitable candidates as drug carriers and solubility enhancers. In this study, the feasibility of MSNs as a carrier of poorly soluble drugs, using prednisolone as a model drug, in ODFs was investigated. Our results revealed that the increased amount of MSNs in ODFs leads to shortening of the disintegration time of the films. Drug content investigations showed that low dose ODFs with prednisolone incorporation efficiencies higher than 80% could be produced. Furthermore, the prednisolone release profile from ODFs can be tuned with the incorporation of MSNs as drug carrier (MSNpred). The MSNpred incorporated ODFs yield with immediate release of drug from the ODF, whereby 90% of the prednisolone content could be released in the first minutes. By modifying the MSNpred design with copolymer surface coating, prednisolone (cop-MSNpred) release can be modulated into a two-step sustained release profile. To sum up, the MSNs platform does not only provide careful low dose incorporation into ODF with high efficiency, but it also aids in tuning the drug release profiles from ODFs.

Evaluation of the Efficacy of Different Concentrations of Dextrose Prolotherapy in Temporomandibular Joint Hypermobility Treatment.

PURPOSE: The aim of this study was to compare and evaluate the efficacy of different concentrations of dextrose prolotherapy for the treatment of temporomandibular joint (TMJ) hypermobility. PATIENTS AND METHODS: A prospective, randomized clinical trial including patients with subluxation or dislocation was performed. The study comprised 40 patients. Patients were randomly divided into 4 groups: control group, 10% dextrose, 20% dextrose, and 30% dextrose group. Patients in all groups received injections into 4 different areas of each TMJ in 4 sessions at monthly intervals. Visual analog scale of TMJ pain intensity, maximum mouth opening (MMO), joint sounds, and frequency of luxations were recorded preoperatively and postoperatively after 1 month of last injection. The collected data were then statistically analyzed. RESULTS: Each group showed postoperatively significant improvement in TMJ pain, significant decrease in both MMO and joint sound. Besides that, TMJ locking was not observed in any patient during the follow-up period. There were no statistically significant differences throughout the study intervals between the groups. CONCLUSION: It was concluded that there was no significant difference between control group and dextrose groups and there is no superiority of any concentration of dextrose over the others in TMJ prolotherapy, and all treatment procedures were efficient in improvement of clinical symptoms related to TMJ hypermobility. If dextrose is used as a proliferant, it can be said that 10% dextrose can be sufficient in TMJ hypermobility treatment.

A tunnel shape defect on maxillary bone after accidental injection of formocresol instead of anesthetic solution.

Accidental injection or leakages of various chemical disinfectants used during root canal preparation into adjacent tissues have been shown to have deleterious effects on surrounding tissue. Formocresol (FC) is an effective intracanal disinfectant used in endodontic procedures. However, it is known to have harmful effects into adjacent tissues. The aim of this article is to present an unusual case in which a 28-year-old male patient developed gingival and bone necrosis after the accidental injection of FC instead of local anesthetic solution for tooth extraction and to review cases in the literature where complications have occurred due to the use of FC.