Use of marine occurrent extracts to enhance the stability of dentin extracellular matrix.

Chitosan (CS) and phloroglucinol (PhG), two extracts abundantly found in marine life, were investigated for their ability to biomodify demineralized dentin by enhancing collagen crosslinks and improving dentin extracellular matrix (ECM) mechanical and biochemical stability. Dentin obtained from non-carious extracted human molars were demineralized with phosphoric acid. Baseline Fourier-transform infrared (FTIR) spectra, apparent flexural elastic modulus (AE) and dry mass (DM) of each specimen were independently acquired. Specimens were randomly incubated for 5 min into either ultrapure water (no-treatment), 1% glutaraldehyde (GA), 1% CS or 1% PhG. Water and GA were used, respectively, as a negative and positive control for collagen crosslinks. Specimens' post-treatment FTIR spectra, AE, and DM were obtained and compared with correspondent baseline measurements. Additionally, the host-derived proteolytic activity of dentin ECM was assessed using hydroxyproline assay (HYP) and spectrofluorometric analysis of a fluorescent-quenched substrate specific for matrix metalloproteinases (MMPs). Finally, the bond strength of an etch-and-rinse adhesive was evaluated after application of marine compounds as non-rinsing dentin primers. Dentin specimens FTIR spectral profile changed remarkably, and their AE increased significantly after treatment with marine compounds. DM variation, HYP assay and fluorogenic substrate analysis concurrently indicated the biodegradation of CS- and PhG-treated specimens was significantly lesser in comparison with untreated specimens. CS and PhG treatments enhanced biomechanical/biochemical stability of demineralized dentin. These novel results show that PhG is a primer with the capacity to biomodify demineralized dentin, hence rendering it less susceptible to biodegradation by host-proteases.

Leveraging machine learning to create user-friendly models to mitigate appointment failure at dental school clinics.

PURPOSE/OBJECTIVES: This study had a twofold outcome. The first aim was to develop an efficient, machine learning (ML) model using data from a dental school clinic (DSC) electronic health record (EHR). This model identified patients with a high likelihood of failing an appointment and provided a user-friendly system with a rating score that would alert clinicians and administrators of patients at high risk of no-show appointments. The second aim was to identify key factors with ML modeling that contributed to patient no-show appointments. METHODS: Using de-identified data from a DSC EHR, eight ML algorithms were evaluated: simple decision tree, bagging regressor classifier, random forest classifier, gradient boosted regression, AdaBoost regression, XGBoost regression, neural network, and logistic regression classifier. The performance of each model was assessed using a confusion matrix with different threshold level of probability; precision, recall and predicted accuracy on each threshold; receiver-operating characteristic curve (ROC) and area under curve (AUC); as well as F1 score. RESULTS: The ML models agreed on the threshold of probability score at 0.20-0.25 with Bagging classifier as the model that performed best with a F1 score of 0.41 and AUC of 0.76. Results showed a strong correlation between appointment failure and appointment confirmation, patient's age, number of visits before the appointment, total number of prior failed appointments, appointment lead time, as well as the patient's total number of medical alerts. CONCLUSIONS: Altogether, the implementation of this user-friendly ML model can improve DSC workflow, benefiting dental students learning outcomes and optimizing personalized patient care.

Plant Cell-Engineered Gold Nanoparticles Conjugated to Quercetin Inhibit SARS-CoV-2 and HSV-1 Entry.

Recent studies have revealed considerable promise in the antiviral properties of metal nanomaterials, specifically when biologically prepared. This study demonstrates for the first time the antiviral roles of the plant cell-engineered gold nanoparticles (pAuNPs) alone and when conjugated with quercetin (pAuNPsQ). We show here that the quercetin conjugated nanoparticles (pAuNPsQ) preferentially inhibit the cell entry of two medically important viruses-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and herpes simplex virus type-1 (HSV-1) using different mechanisms. Interestingly, in the case of SARS-CoV-2, the pre-treatment of target cells with pAuNPsQ inhibited the viral entry, but the pre-treatment of the virus with pAuNPsQ did not affect viral entry into the host cell. In contrast, pAuNPsQ demonstrated effective blocking capabilities against HSV-1 entry, either during the pre-treatment of target cells or by inducing virus neutralization. In addition, pAuNPsQ also significantly affected HSV-1 replication, evidenced by the plaque-counting assay. In this study, we also tested the chemically synthesized gold nanoparticles (cAuNPs) of identical size and shape and observed comparable effects. The versatility of plant cell-based nanomaterial fabrication and its modification with bioactive compounds opens a new frontier in therapeutics, specifically in designing novel antiviral formulations.

In vitro assessment of antimicrobial potential of low molecular weight chitosan and its ability to mechanically reinforce and control endogenous proteolytic activity of dentine.

AIMS: Chitosan-based biomaterials exhibit several properties of biological interest for endodontic treatment. Herein, a low molecular weight chitosan (CH) solution was tested for its antimicrobial activity against Enterococcus faecalis (E. faecalis) and effects on dentine structure. METHODOLOGY: The root canal of 27 extracted uniradicular teeth were biomechanically prepared, inoculated with a suspension of E. faecalis and randomly assigned to be irrigated with either 5.25% sodium hypochlorite (NaClO), 0.2% CH or sterile ultrapure water (W). Bacteriologic samples were collected from root canals and quantified for of E. faecalis colony-forming units (CFUs). The effectiveness of CH over E. faecalis biofilms was further measured using the MBEC Assay®. Additionally, dentine beams and dentine powder were obtained, respectively, from crowns and roots of 20 extracted third molars. Dentine samples were treated or not with 17% EDTA and immersed in either CH or W for 1 min. The effects of CH on dentine structure were evaluated by assessment of the modulus of elasticity, endogenous proteolytic activity and biochemical modifications. RESULTS: The number of E. faecalis CFUs was significantly lower for samples irrigated with CH and NaClO. No significant differences were found between CH and NaClO treatments. Higher modulus of elasticity and lower proteolytic activity were reported for dentine CH-treated specimens. Chemical interaction between CH and dentine was observed for samples treated or not with EDTA. CONCLUSIONS: Present findings suggest that CH could be used as an irrigant during root canal treatment with the triple benefit of reducing bacterial activity, mechanically reinforcing dentine and inhibiting dentine proteolytic activity.

Assessment of dental ergonomics among dental students: A retrospective study.

INTRODUCTION: Musculoskeletal (MSK) disorders account for 11%-98% of occupational health issues for dental professionals, with an onset as early as in dental school. Dental ergonomics is among the risk factors; thus, a prompt assessment is crucial in preventing future MSK pain. The aim of this study was to retrospectively assess dental ergonomics of second-year dental students after dedicated lectures were introduced in the predoctoral curriculum. METHODS: Three cohorts of second-year dental students were evaluated during preclinical activity in July 2019, January 2022, and December 2022 by an Occupational Therapy (OT) faculty and calibrated OT students. Dental ergonomics was assessed with the Rapid Upper Limb Assessment (RULA). Dental student cohorts were compared with one-way analysis of variance (ANOVA). RESULTS: The average RULA final score of 409 participants was 5.1 ± 0.9, with no difference between the three cohorts (p = 0.676). The January 2022 cohort scored significantly lower in wrist-arm score than that of 2019 (p = 0.001) and December 2022 (p = 0.046). Neck and lower limb posture were significantly higher in January 2022 cohort than in 2019 (p = 0.001 and 0.013) and December 2022 (p = 0.001 and 0.005) cohorts. The December 2022 cohort revealed a medium, high and extremely high risk of developing MSK of 40.2%, 37.1%, and 21.6%, respectively, with no difference between sexes. CONCLUSION: The risk of developing MSK pain was medium-high in predoctoral dental students and was not related to sex. The overall dental ergonomics required attention and rapid change. Further implementation of varied forms of teaching and monitoring of dental ergonomics from the early years of education is recommended to prevent development of MSK pain at young age and foster better postural habits.

Dentin primer based on a highly functionalized gelatin-methacryloyl hydrogel.

Gelatin-methacryloyl hydrogels (GelMA) have demonstrated their utility as scaffolds in a variety of tissue engineering applications. OBJECTIVES: In this study, a highly functionalized GelMA hydrogel was synthesized and assessed for degree of functionalization. As the proposed GelMA hydrogel was coupled to a visible-light photoinitiator, we hypothesized it might serve as base to formulate a model dentin primer for application in restorative dentistry. METHODS: GelMA was mixed with photoinitiator lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP), photopolymerized for 0-40 s using a dental light-curing device and tested for extrudability, degree of photo-crosslinking (DPxlink), water sorption/solubility/swelling (WS/SL/SW) and apparent modulus of elasticity (AE). Model dentin primer was prepared by mixing GelMA+LAP with a primer of a commercial three-step etch-and-rinse adhesive. After application of GelMA-based primer to acid-etched dentin, samples were bonded with correspondent adhesive agent, photopolymerized and had their immediate bond strength compared to control samples primed and bonded with the same commercial material. RESULTS: Extrudability of hydrogel was confirmed using a microsyringe to write the acronym "CDMI". DPxlink of GelMA+LAP changed significantly as a function of photopolymerization time (20 s < 30 s ≤ 40 s). WS, SL and SW were significantly reduced in hydrogels polymerized for 30 and 40 s. AE of hydrogels varied significantly as a function of photopolymerization time (20 s < 30 s ≤ 40 s; 20 s ‡ 40 s). Bond strength of dentin primed with GelMA-based primer was lower (∼29.3 MPa) but not significantly of that of control (∼34.6 MPa). CONCLUSIONS: Optimization of a GelMA-based dentin primers can lead to the development of promising biomimetic adhesives for dentin rehabilitation.

Early detection of oral potentially malignant disorders using machine learning: a retrospective pilot study.

Early diagnosis of oral potentially malignant disorders (OPMDs) may be hindered by similar clinical presentations shared between benign oral lesions and OPMDs. The goal of this retrospective pilot study was to assess the use of machine learning (ML) as an adjunctive evaluation in conjunction with conventional comprehensive oral examination of OMPDs. Digital images of 80 deidentified intraoral lesions (40 benign intraoral lesions and 40 OPMDs) were collected. The images, which were previously identified independently by experienced oral pathologists, were used to create 3 datasets: raw images, grayscale images, and enhanced color images. The datasets were subsequently divided into training (n = 60), test (n = 10), and validation (n = 10) groups so that class labels (benign lesion or OMPD) were distributed equally in each group. A cross-validated grid search was used to optimize the hyperparameters of the Extreme Gradient Boosting (XGBoost) classifications model. Predictions were made on the test group and used to optimize the prediction threshold. The final results were validated by predictions based on the validation group. The XGBoost classification model was able to differentiate between benign intraoral lesions and OPMDs with a mean classification accuracy of 70%, sensitivity of 80%, and specificity of 60% when grayscale and enhanced color intraoral images were used. A mean classification accuracy of 50%, sensitivity of 40%, and specificity of 60% were observed when raw intraoral images were used. The results demonstrated that ML may be a promising tool for the diagnosis of OPMDs when used as an adjunct to conventional comprehensive oral examination.

Significance of chlorine-dioxide-based oral rinses in preventing SARS-CoV-2 cell entry.

OBJECTIVE: This work aims to determine the efficacy of preprocedural oral rinsing with chlorine dioxide solutions to minimize the risk of coronavirus disease 2019 (COVID-19) transmission during high-risk dental procedures. METHODS: The antiviral activity of chlorine-dioxide-based oral rinse (OR) solutions was tested by pre-incubating with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pseudovirus in a dosage-dependent manner before transducing to human embryonic kidney epithelial (HEK293T-ACE2) cells, which stably expresses ACE-2 receptor. Viral entry was determined by measuring luciferase activity using a luminescence microplate reader. In the cell-to-cell fusion assay, effector Chinese hamster ovary (CHO-K1) cells co-expressing spike glycoprotein of SARS-CoV-2 and T7 RNA polymerase were pre-incubated with the ORs before co-culturing with the target CHO-K1 cells co-expressing human ACE2 receptor and luciferase gene. The luciferase signal was quantified 24 h after mixing the cells. Surface expression of SARS-CoV-2 spike glycoprotein and ACE-2 receptor was confirmed using direct fluorescent imaging and quantitative cell-ELISA. Finally, dosage-dependent cytotoxic effects of ORs were evaluated at two different time points. RESULTS: A dosage-dependent antiviral effect of the ORs was observed against SARS-CoV-2 cell entry and spike glycoprotein mediated cell-to-cell fusion. This demonstrates that ORs can be useful as a preprocedural step to reduce viral infectivity. CONCLUSIONS: Chlorine-dioxide-based ORs have a potential benefit for reducing SARS-CoV-2 entry and spread.

Shear Bond Strength and Color Stability of Novel Antibacterial Nanofilled Dental Adhesive Resins.

Experimental adhesives containing co-doped metaloxide nanoparticles were demonstrated to display strong and long-term antibacterial properties against Streptococcus mutans biofilms. The present study represents an effort to characterize the shear-bond strength (SBS) and color stability (CS) of these novel biomaterials. Experimental adhesives were obtained by dispersing nitrogen and fluorine co-doped titanium dioxide nanoparticles (NF_TiO2, 10%, 20% or 30%, v/v%) into OptiBond Solo Plus (OPTB). Dentin surfaces were wet-polished (600-Grit). Specimens (n = 5/group) of Tetric EvoCeram were fabricated and bonded using either OPTB or experimental (OPTB + NF_TiO2) adhesives. Specimens were stored in water (37 °C) for twenty-four hours (T1), three months (T2), and six months (T3). At T1, T2, or T3, specimens were removed from water storage and were tested for SBS. Disc-shaped specimens (n = 10/group; d = 6.0 mm, t = 0.5 mm) of adhesives investigated were fabricated and subjected to thermocycling (10,000 cycles, 5−55 °C, 15 s dwell time). Specimens' colors were determined with a VITA Easyshade® V spectrophotometer (after every 1000 cycles). SBS data was analyzed using two-way ANOVA and post-hoc Tukey tests, while CS data was analyzed using one-way ANOVA and post-hoc Tukey tests (α = 0.05). Mean values of SBS ranged from 16.39 ± 4.20 MPa (OPTB + 30%NF_TiO2) to 19.11 ± 1.11 MPa (OPTB), from 12.99 ± 2.53 MPa (OPTB + 30% NF_TiO2) to 14.87 ± 2.02 (OPTB) and from 11.37 ± 1.89 (OPTB + 20% NF_TiO2) to 14.19 ± 2.24 (OPTB) after twenty-four hours, three months, and six months of water storage, respectively. Experimental materials had SBS values that were comparable (p > 0.05) to those from OPTB independently of nanoparticle concentration or time-point considered. Experimental materials with higher NF_TiO2 concentrations had less intense color variations and were more color stable than OPTB even after 10,000 thermocycles. In combination, the results reported have demonstrated that experimental adhesives can establish strong and durable bonds to human dentin while displaying colors that are more stable, thereby suggesting that the antibacterial nanotechnology investigated can withstand the harsh conditions within the oral cavity without compromising the esthetic component of dental restorations.

Changes to dentin extracellular matrix following treatment with plant-based polyphenols.

This study investigated whether treatment with plant-based polyphenols (PB-P) affected the biochemical and/or biomechanical properties of dentin extracellular matrix (ECM). Three PB-Ps were evaluated: luteolin (LT), galangin (GL), and proanthocyanidin (PAC). Because dentin ECM requires demineralization before treatment, this study also assessed the effect of these PB-Ps on dentin demineralized by two different chemicals. Dentin samples from extracted third molars were obtained, sectioned, and randomly assigned for demineralization with either phosphoric acid (PA) or ethylenediaminetetraacetic acid (EDTA). Following demineralization, baseline infrared (IR) spectra and apparent elastic modulus (AE) of each specimen were independently acquired. Based upon these initial tests, samples were randomly assigned to one of the PB-P treatments to ensure that distribution of baseline AE was similar across treatment groups. IR and AE specimens were individually immersed in either 0.2% LT, 0.4% GL or 1% PAC for 2 min. IR spectra of treated samples were compared to baseline IR spectra, looking for any interaction of PB-Ps with the demineralized dentin. The IR spectrum and AE of each PB-P-treated specimen were compared with their own correspondent baseline measurement. The ability of PB-Ps to inhibit proteolytic activity of dentin ECM was assessed by the hydroxyproline assay. Finally, the effect of PB-Ps on immediate bond strength of a dental adhesive to PA- or EDTA-etched dentin was also evaluated. PB-Ps exhibited distinctively binding affinity to dentin ECM and promoted significant increase in AE. PB-P treatment reduced the degradation rate of dentin ECM without causing detrimental effect on immediate bond strength to dentin. Our work represents the first-time that LT and GL have been assessed as dentin ECM biomodifiers.

ICP-MS measurements of elemental release from two palladium alloys into a corrosion testing medium for different solution volumes and agitation conditions.

STATEMENT OF PROBLEM: The in vivo release of Pd from palladium alloys into the oral environment and sensitivity reactions by patients has been of concern. However, little information is available about the variation in elemental release from different palladium alloys. PURPOSE: The purpose of this in vitro study was to compare the elemental release into a corrosion-testing medium from a high-palladium alloy (Freedom Plus, 78Pd-8Cu-5Ga-6In-2Au) and a Pd-Ag alloy (Super Star, 60Pd-28Ag-6In-5Sn) under different conditions. MATERIAL AND METHODS: Alloys were cast into Ø12×1-mm-thick disks, subjected to simulated porcelain-firing heat treatment, polished, and ultrasonically cleaned in ethanol. Three specimens of each alloy were immersed for 700 hours in a solution for in vitro corrosion testing (ISO Standard 10271) that was maintained at 37 °C. Two solution volumes (125 mL and 250 mL) were used, and the solutions were subjected to either no agitation or agitation. Elemental compositions of the solutions were analyzed by using inductively coupled plasma-mass spectroscopy (ICP-MS). Concentrations of released elements from each alloy for the 2 solution volumes and agitation conditions were compared by using the restricted maximum likelihood estimation method with a 4-way repeated-measures ANOVA, the Satterwhite degrees of freedom method, a lognormal response distribution, and the covariance structure of compound symmetry. RESULTS: For the 4 combinations of solution volume and agitation conditions, the mean amount of palladium released was 3 orders of magnitude less for the Pd-Ag alloy (0.009 to 0.017 µg/cm2 of alloy surface) compared with the Pd-Cu-Ga alloy (17.9 to 28.7 µg/cm2). Larger mean amounts of Sn, Ga, Ag, and In (0.29 to 0.39, 0.57 to 0.83, 0.71 to 1.08, and 0.91 to 1.25 µg/cm2, respectively) compared with Pd were released from the Pd-Ag alloy. Smaller amounts of Cu, Ga, and In (4.8 to 9.9, 5.9 to 12.8, and 4.2 to 9.5 µg/cm2, respectively) compared with Pd were released from the Pd-Cu-Ga alloy. The Ru released was much lower for the Pd-Ag alloy (0.002 µg/cm2) than the Pd-Cu-Ga alloy (0.032 to 0.053 µg/cm2). Statistically significant differences (P<.001) in elemental release were found for the factors of alloy and element and the alloy×element interaction. Significant differences were found for the solution volume (P=.022), solution volume×element interaction (P=.022), and alloy×solution volume×element interaction (P=.004). No significant effect was found for agitation condition. CONCLUSIONS: The relative amounts of released elements from each alloy were not proportional to the relative amounts in the composition. The amounts of Pd and Ga released from the Pd-Cu-Ga alloy were consistent with the breakdown of a Pd2Ga microstructural phase and perhaps some dissolution of the palladium solid solution matrix. Precipitates, rather than the palladium solid solution matrix, appeared to undergo greater dissolution in the Pd-Ag alloy. The Pd-Ag alloy should have lower risk of adverse biological reactions than the Pd-Cu-Ga alloy.

Ultrasonic scaling in COVID-era dentistry: A quantitative assessment of aerosol spread during simulated and clinical ultrasonic scaling procedures.

OBJECTIVE: Healthcare agencies recommend limited use of aerosol-generating procedures to mitigate disease (COVID-19) transmission. However, total dispersion patterns of aerosols, particularly respirable droplets, via dental ultrasonic units is unclear. The purpose of this study was to characterize and map total spatter, droplet and aerosol dispersion during ultrasonic scaling in simulated and clinical contexts. METHODS: Ultrasonic scaling was performed on dental simulation units using methylene blue dye-stained water. All resultant stain profiles were photoanalysed to calculate droplet size and travel distance/direction. Airborne particle concentrations were also documented 0-1.2 m (0-4ft.) and 1.2-2.4 m (4-8ft.) from patients during in vivo ultrasonic scaling with a saliva ejector. RESULTS: Stain profiles showed droplets between 25 and 50µm in diameter were most common, with smaller droplets closer to the mouth. In-vivo particle concentrations were uniformly low. The smallest (<1 µm, PM1) and largest (>10 µm, PM10+) particles were most common, especially within 1.2 m (4ft.) of the patient. Respirable particles (PM2.5) were uncommon. CONCLUSIONS: Tests showed the highest concentration of small droplets in zones nearest the patient. While uncommon, particles were detected up to 2.4 m (8ft.) away. Furthermore, observed particle sizes were consistent with those that can carry infectious agents. Efforts to mitigate the spread of inhalable aerosols should emphasize proximate regions nearest the procedure, including personal protective equipment and the use of evacuation devices.

A scoping review of surgical masks and N95 filtering facepiece respirators: Learning from the past to guide the future of dentistry.

With the 2019 emergence of coronavirus disease 19 (colloquially called COVID-19) came renewed public concern about airborne and aerosolized virus transmission. Accompanying this concern were many conflicting dialogues about which forms of personal protective equipment best protect dental health care practitioners and their patients from viral exposure. In this comprehensive review we provide a thorough and critical assessment of face masks and face shields, some of the most frequently recommended personal safeguards against viral infection. We begin by describing the function and practicality of the most common mask types used in dentistry: procedural masks, surgical masks, and filtering respirator facemasks (also called N95s). This is followed by a critical assessment of mask use based on a review of published evidence in three key domains: the degree to which each mask type is shown to protect against airborne and aerosolized disease, the reported likelihood for non-compliance among mask users, and risk factors associated with both proper and improper mask use. We use this information to conclude our review with several practical, evidence-based recommendations for mask use in dental and dental educational clinics.

Bioactive glass-containing hydrogel delivery system for osteogenic differentiation of human dental pulp stem cells.

Osteoconductive hydrogels can be fabricated by incorporating necessary growth factors and bioactive particles or simply utilizing the ability of the hydrogel itself to induce bone regeneration. The osteogenic inductive potential of the bioactive glass microparticles (BG MPs) has been well-studied. However, the role of the hydrogel embedding the BG MPs on the osteogenic differentiation of the encapsulated stem cells has not been well established. Moreover, it has been reported that the dental pulp stem cell (DPSC) has the capability of regenerating the craniofacial bone tissue when receiving the necessary osteogenic signals from the microenvironment. In the current study, we have fabricated a composite hydrogel based on alginate and Matrigel containing BG MPs and evaluated the role of the BG MPs and Matrigel on osteogenic differentiation of the encapsulated DPSCs. Our results confirmed that presence of Matrigel enhances the osteogenic differentiation of the DPSCs regardless of the decrease in elasticity of the hydrogel in presence of the BG MPs. This strategy of modifying the microenvironment can be a promising approach for craniofacial bone tissue engineering.

Comparison of 2 self-adhesive resin cements with or without a self-etching primer.

Self-adhesive resin cements that eliminate the primer step have been introduced to simplify the bonding protocol for indirect restorations. The aim of the present study was to compare the shear bond strengths (SBSs) of 2 self-adhesive resin cements used with or without a self-etching primer. The hypothesis was that adding a separate primer component to the self-adhesive systems would increase the SBS at the tooth-adhesive interface. One hundred twenty extracted human molars were hemisectioned and embedded in epoxy. Specimens were polished to expose enamel or dentin surfaces and randomly assigned to 12 test groups (n = 20). The tested variables were (1) the type of bonded tissue (enamel or dentin); (2) the cement used; (3) whether the cement was applied with or without a primer; (4) and whether the primer was air dried or photopolymerized. Bonding jigs were used to apply the self-adhesive resin cement to the tooth surfaces. A 2-minute self-cure was followed by 20 seconds of light curing. Specimens were stored in water for 24 hours and then subjected to SBS testing in a universal testing machine. Fractured specimens were examined under a microscope to determine the modes of failure. Mean SBS values were compared using a paired Student t test (with post hoc Tukey test) and an analysis of variance (α = 0.05). Compared to the control groups, the air-dried primer groups showed SBSs that were 4-6 times greater for the specimens bonded to dentin and 2-3 times greater for specimens bonded to enamel. The photopolymerized primer groups followed the same trend. The photopolymerized groups showed higher percentages of cohesive tooth failure than did air-dried primer groups. Placement of a self-etching primer prior to a self-adhesive resin cement significantly increased the SBS to tooth structure of the "all-in-1" resin cements that were tested. Photopolymerizing the primer did not significantly increase the bond strength.

Myristic Acid Coated Protein Immobilised Mesoporous Silica Particles as pH Induced Oral Delivery System for the Delivery of Biomolecules.

Solid core drug delivery systems (SCDDS) were prepared for the oral delivery of biomolecules using mesoporous silica as core, bovine haemoglobin (bHb) as model drug and supercritical fluid (SCF) processing as encapsulation technique. The use of organic solvents or harsh processing conditions in the development of drug delivery systems for biomolecules can be detrimental for the structural integrity of the molecule. Hence, the coating on protein-immobilised particles was performed via supercritical carbon dioxide (scCO2) processing at a temperature lower than the melting point of myristic acid (MA) to avoid any thermal degradation of bHb. The SCDDS were prepared by bHb immobilisation on mesoporous silica followed by myristic acid (MA) coating at 43 °C and 100 bar in scCO2. bHb-immobilised silica particles were also coated via solvent evaporation (SE) to compare the protein release with scCO2 processed formulations. In both cases, MA coating provided required enteric protection and restricted the bHb release for the first two hours in simulated gastric fluid (SGF). The protein release was immediate upon the change of media to simulated intestinal fluid (SIF), reaching 70% within three hours. The release from SCF processed samples was slower than SE formulations, indicating superior surface coverage of MA on particles in comparison to the SE method. Most importantly, the protein conformation remained unchanged after the release from SCDDS as confirmed by circular dichroism. This study clearly demonstrates that the approach involving protein immobilisation on silica and scCO2 assisted melt-coating method can protect biomolecules from gastric environment and provide the required release of a biologic in intestine without any untoward effects on protein conformation during processing or after release.

Development and evaluation of performance characteristics of timolol-loaded composite ocular films as potential delivery platforms for treatment of glaucoma.

Thin and erodible polymeric films were developed as potential ocular drug delivery systems to increase drug retention on the eye with the aim of improving bioavailability and achieving controlled drug release. Two biocompatible film forming polymers, hyaluronic acid (HA) and hydroxypropyl methylcellulose (HPMC), which are currently used as thickening agents in eye drops were employed. Two different films were prepared (i) as single polymer and (ii) as composite formulations by solvent casting method, incorporating glycerol (GLY) as plasticizer and timolol maleate (TM) as model glaucoma drug. After preliminary optimization of transparency and ease of handling, the formulations were further characterized for their physicochemical properties. No indication of significant drug-polymer or polymer-polymer (in composite films) interaction was observed from FTIR results while evaluation by IR mapping revealed uniform distribution of drug throughout the films. Amorphization of TM in the film matrix was confirmed by both DSC and XRD. Swelling studies illustrated remarkable swelling capacity of HA in comparison with HPMC which directly affected the drug release profiles, making HA a suitable polymer for controlled ocular drug delivery. Tensile and mucoadhesion properties confirmed higher elasticity and adhesiveness of HA while HPMC produced stronger films. The effect of sterilization by UV radiation on mechanical properties was also evaluated and showed no significant difference between the sterilized and non-sterilized films. The SEM results confirmed smoothness and homogeneity of film surfaces for all the formulations studied. The in vitro drug dissolution studies showed more extended release profiles of formulations containing HA. Cytotoxicity study (cell viability) using MTT assay on HeLa cells, confirmed that the single polymer and composite films are generally safe for ocular administration. The present work shows excellent film forming ability of HA and HPMC which can be used as single polymer or combined in composite formulations as potential topical ocular drug delivery platform to enhance drug retention on the ocular surface and therefore potential improved bioavailability.

Prediction of human intestinal absorption using micellar liquid chromatography with an aminopropyl stationary phase.

The extent of human intestinal absorption (HIA) for a drug is considered to be an important pharmacokinetic parameter which must be determined for orally administered drugs. Traditional experimental methods relied upon animal testing and are renowned for being time consuming and expensive as well as being ethically unfavourable. As a result, the development of alternative methods to evaluate a drug's pharmacokinetics is crucial. Micellar liquid chromatography is considered to be one of these methods that can replace the use of animals in the prediction of HIA. In this study, the combination of an aminopropyl column with the biosurfactant sodium deoxycholate bile salt was used in the experimental determination of micelle-water partition coefficients (log Pmw ) for a group of compounds. Multiple linear regression was then used for the prediction of HIA using the experimentally determined log Pmw along with other molecular descriptors, leading to the construction of a model equation of R2 = 85% and a prediction power represented by R2 Pred. = 72%. The use of micellar liquid chromatography with an aminopropyl column in combination with sodium deoxycholate was found to be a good method for the prediction of human intestinal absorption, providing data for a far wider range of compounds compared with previous studies.

Formation of a Bile Salt-Drug Hydrogel to Predict Human Intestinal Absorption.

The unique character of bile salts to self-assemble into hydrogels in the presence of halide salts was exploited in this work to facilitate the prediction of human intestinal absorption (%HIA) for a set of 25 compounds. This was achieved by firstly incorporating each compound separately within the process of gel formation to create a series of gel-drug membranes. Scanning electron microscopy analysis of the freeze-dried samples of the blank bile salt hydrogels and drug-loaded bile salt hydrogels indicated a unique microstructure made of a network of intertwined fibrils. Drug-loaded sodium deoxycholate hydrogels were then utilized as the donor phase to study permeability using flow-through and static diffusion cells. The resulting values of the release-permeability coefficient (Kp) were then analyzed, along with other molecular descriptors, for the %HIA using multiple linear regression. Overall, when comparing predicted values (using the systems presented in this study) with known literature values, it can be seen that both methods (i.e., using static and flow-through cells) had good predictability with R2PRED values of 79.8% and 79.7%, respectively. This study therefore proposes a novel, accurate, and precise way to predict HIA for compounds of pharmaceutical interest using a simple in vitro permeation system. It is important to develop alternatives to the current methods used in prediction of HIA, which are expensive and time-consuming or include the use of animals. Therefore, the proposed method in this study being economic and time-saving provides superiority over these current methods and suggests the possibility of its use as an alternate to such methods for prediction of HIA.