Antibacterial efficacy and drug-induced tooth discolouration of antibiotic combinations for endodontic regenerative procedures.

Elimination of microbial contamination from the root canal system is a precondition for successful root canal treatment. Teeth with immature root development, necrotic pulps and apical periodontitis present multiple challenges for successful treatment. Disinfection is achieved by irrigation followed by the placement of an intracanal medicament. A mixture of ciprofloxacin, metronidazole and minocycline (3-MIX S) has been shown to be very effective in eliminating endodontic pathogens in vitro and in vivo. Among the components of the mixture, minocycline can induce tooth discolouration after long-term oral use. Therefore, the elimination of minocycline from the above-mentioned combination has been suggested to prevent the occasion of this undesirable effect. The aim of this study was to investigate the potential antimicrobial efficacy of alternative antibiotic combinations [3-MIX C (clarithromycin); 3-MIX F (fosfomycin)] against bacteria from infected root canals. An additional objective was to evaluate their discolouration potential as possible alternatives to minocycline-based intracanal medicaments. Our in vitro results clearly demonstrated that 3-MIX C and 3-MIX F had a greater antimicrobial activity than 3-MIX S, underlying that clarithromycin still had a higher capacity to kill endodontic pathogens in vitro compared to fosfomycin. Both 3-MIX C and 3-MIX F were able to avoid the permanent staining effect of the crown

Evaluation of the bactericidal activity of a hyaluronic acid-vehicled clarithromycin antibiotic mixture by confocal laser scanning microscopy

Confocal laser scanning microscopy (CLSM) was used to evaluate the antibacterial effect and depth of action of a novel clarithromycin-containing triple antibiotic mixture, which was proposed for root canal disinfection in dental pulp regeneration. A previous study reported that this mixture had no tooth discoloration effects in vitro. After infection with Enterococcus faecalis for 3 weeks, the dentinal tubules in the cylindrical root specimens were exposed to different antibiotic mixtures: ciprofloxacin, metronidazole and minocycline (3-MIX); ciprofloxacin, metronidazole and clarithromycin (3-MIXC) and ciprofloxacin and metronidazole (2-MIX). Each antibiotic formulation was mixed with macrogol (MG) or hyaluronic acid (HA) vehicles. CLSM and viability staining were used to quantitatively analyze the mean depth of the antibacterial effect and the proportions of dead and live bacteria inside the dentinal tubules. The 3-MIX and 3-MIXC demonstrated a similar depth of action. The mean proportion of dead bacteria was similar in the 3-MIX and 3-MIXC groups, and both were statistically higher than that of 2-MIX (p = 0.014). Each antibiotic mixture showed a higher bactericidal efficacy if conveyed with HA, compared to MG (3-MIX, p = 0.019; 3-MIXC, p = 0.013 and 2-MIX, p = 0.0125). The depth of action and the antibacterial efficacy of 3-MIXC seemed comparable with 3-MIX

Polymersome-Mediated Delivery of Combination Anticancer Therapy to Head and Neck Cancer Cells: 2D and 3D in Vitro Evaluation

Polymersomes have the potential to encapsulate and deliver chemotherapeutic drugs into tumor cells, reducing off-target toxicity that often compromises anticancer treatment. Here, we assess the ability of the pH-sensitive poly 2-(methacryloyloxy)ethyl phosphorylcholine (PMPC)- poly 2-(diisopropylamino)ethyl methacrylate (PDPA) polymersomes to encapsulate chemotherapeutic agents for effective combinational anticancer therapy. Polymersome uptake and ability to deliver encapsulated drugs into healthy normal oral cells and oral head and neck squamous cell carcinoma (HNSCC) cells was measured in two and three-dimensional culture systems. PMPC-PDPA polymersomes were more rapidly internalized by HNSCC cells compared to normal oral cells. Polymersome cellular uptake was found to be mediated by class B scavenger receptors. We also observed that these receptors are more highly expressed by cancer cells compared to normal oral cells, enabling polymersome-mediated targeting. Doxorubicin and paclitaxel were encapsulated into pH-sensitive PMPC-PDPA polymersomes with high efficiencies either in isolation or as a dual-load for both singular and combinational delivery. In monolayer culture, only a short exposure to drug-loaded polymersomes was required to elicit a strong cytotoxic effect. When delivered to three-dimensional tumor models, PMPC-PDPA polymersomes were able to penetrate deep into the center of the spheroid resulting in extensive cell damage when loaded with both singular and dual-loaded chemotherapeutics. PMPC-PDPA polymersomes offer a novel system for the effective delivery of chemotherapeutics for the treatment of HNSCC. Moreover, the preferential internalization of PMPC polymersomes by exploiting elevated scavenger receptor expression on cancer cells opens up the opportunity to target polymersomes to tumors

Safety Assessment of Pharmaceutical Distribution in a Hospital Environment

Many of the catastrophic errors in health care are related to inadequate procedures. Robust preventative actions are therefore required to minimize the risks inherent to the prescribing, dispensing and administration of medicines. The redesigning of subsystem processes is a goal that should be undertaken to improve the overall safety of hospitals. Many organizations are beginning to apply traditional aerospace engineering methodologies to the study of patient safety. In a hospital setting, the pharmacy department is responsible for the procurement, distribution, and control of all medicines used within the organization. Pharmacists should ensure that medicines are delivered to patient care areas in a safe and secure manner and that they are available to the administration within a time frame that meets the essential needs of patients. A Failure mode analysis applied to pharmaceutical distribution has been carried out in the S.G.Battista Hospital in Turin (Italy), from the receiving of the goods stage to the delivery to the departments. Two main high risk activities have been identified from risk matrices and risk priority number analysis. The first activity concerns the picking and packing phases and the second one is due to the low efficiency of the random controls of pharmacists. The analysis has also pointed out some medium risk activities in the refill request control, storage temperature control and consignment to delivery service departments. The present analysis has offered the opportunity of quantifying safety within a specific hospital environment and of designing feasible corrective actions. The real effectiveness of the proposed actions will be verified during a subsequent experimental phase

Safety Assessment of Pharmaceutical Distribution in a Hospital Environment

Many of the catastrophic errors in health care are related to inadequate procedures. Robust preventative actions are therefore required to minimize the risks inherent to the prescribing, dispensing and administration of medicines. The redesigning of subsystem processes is a goal that should be undertaken to improve the overall safety of hospitals. Many organizations are beginning to apply traditional aerospace engineering methodologies to the study of patient safety. In a hospital setting, the pharmacy department is responsible for the procurement, distribution, and control of all medicines used within the organization. Pharmacists should ensure that medicines are delivered to patient care areas in a safe and secure manner and that they are available to the administration within a time frame that meets the essential needs of patients. A Failure mode analysis applied to pharmaceutical distribution has been carried out in the S.G.Battista Hospital in Turin (Italy), from the receiving of the goods stage to the delivery to the departments. Two main high risk activities have been identified from risk matrices and risk priority number analysis. The first activity concerns the picking and packing phases and the second one is due to the low efficiency of the random controls of pharmacists. The analysis has also pointed out some medium risk activities in the refill request control, storage temperature control and consignment to delivery service departments. The present analysis has offered the opportunity of quantifying safety within a specific hospital environment and of designing feasible corrective actions. The real effectiveness of the proposed actions will be verified during a subsequent experimental phas