Drug release kinetics and biological properties of a novel local drug carrier system.

BACKGROUND: The purpose of this in vitro study was to investigate drug release kinetics and cytotoxicity of a novel drug delivery system for treatment of periodontitis. MATERIALS AND METHODS: This in vitro study addresses the fabrication of a polycaprolactone/alginic acid-based polymeric film loaded with metronidazole, as a basic drug in the treatment of periodontal diseases. Films were prepared by solvent casting technique. Four formulations with different percentages of drug by weight (3%, 5%, 9%, and 13%) were prepared. Drug release kinetics were investigated using ultraviolet-visible spectroscopy during (one week). Data were analyzed using repeated measures ANOVA. Cytotoxicity of drug-loaded system extracts was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay using L929 cells after 24-h incubation. The results were evaluated according to ISO standard 10993-5 and assessed using ANOVA and Tukey's tests at a significance level of P < 0.05. RESULTS: All polymeric films showed a burst drug release followed by a gradual release. Drug release data were fitted well with the first-order kinetic model in all drug-containing formulations indicating that drug release is a fraction of remaining drug in the matrix. Drug release is mainly driven by diffusion of medium into the composite matrix. 3%wt metronidazole-containing formulation exhibited the best MTT result. CONCLUSION: The findings of this study supported the synthesis of drug-loaded periodontal films with 3% metronidazole due to better biological properties along with the ability of acceptable drug release to eradicate anaerobic periodontal bacteria.

Facile Synthesis and Characterization of Ibuprofen-mesoporous Hydroxyapatite Nanohybrid as a Sustained Drug Delivery System.

The present study deals with the fabrication of ibuprofen-mesoporous hydroxyapatite (IBU-MHA) particles via the incorporation of ibuprofen (IBU)-as a nonsteroidal anti-inflammatory drug-into mesoporous hydroxyapatite nanoparticles (MHANPs) using an impregnation process, as a novel drug delivery device. MHANPs were synthesized by a self-assembly process using cetyltrimethylammonium bromide (CTAB) as a cationic surfactant and 1-dodecanethiol as a pore expander under basic condition. The focus of the present study was to optimize the incorporation of IBU molecules into MHANPs under different loading conditions. The synthesized MHANPs and IBU-MHA particles were confirmed by X-ray diffraction (XRD), fourier-transform infrared spectroscopy (FTIR), brunauer-emmett-teller (BET), transmission electron microscopy (TEM), and thermal analysis (TGA). Drug loading (DL) efficiency of IBU-MHA particles was determined by ultraviolet-visible (UV-Vis) spectroscopy, and indicated that the optimized IBU-MHA particles with high DL (34.5%) can be obtained at an IBU/ MHANPs ratio of 35/50 (mg/mg), impregnation period of 24 h, and temperature of 40 °C using ethanol as solvent. In-vitro drug release test was carried out to prove the efficiency of IBU-MHA particles as a sustained drug delivery system. A more sustained and controlled drug release was observed for this particles, indicating that it may be have good potential as drug reservoirs for local drug release.

Efficacy of diode laser irradiation during dental bleaching in preventing enamel damage caused by bleaching.

BACKGROUND: Evidence on the protecting effect of laser on bleached enamel is scarce and controversial. Therefore, we aimed to test for the first time whether different wavelengths of diode laser (810 and 980 nm) can prevent enamel surface corrosion. We also tested for the first time whether such therapeutic effects of laser are limited to specific "laser-activated" bleaching gels or both conventional and laser-activated gels. MATERIALS AND METHODS: In this qualitative experimental study, ten intact human teeth were randomly assigned to five Groups. They were sectioned into twenty buccal/lingual pieces. The groups were: (1) laser-activated gel + 810 nm laser, (2) laser-activated gel + 980 nm laser, (3) conventional gel + 810 nm laser, (4) conventional gel + 980 nm laser, (5) conventional gel only, and (6) laser-activated gel - no irradiation. Buccal sections in each group were subjected to bleaching (according to the stated protocols), and later subjected to field-emission scanning electron microscopy (SEM) and X-ray diffraction (XRD). The lingual pieces were used as "before-treatment" negative controls for XRD. RESULTS: XRD showed an increase in the mineral phase and crystallinity of the enamel in all bleaching groups. This was stronger in the laser-irradiated groups with conventional bleaching agent. SEM showed a complete etched surface in the positive control groups (i.e., bleached using conventional agent). However, all four laser groups had almost intact surfaces. CONCLUSION: This study showed the positive effect of diode laser irradiation at 810 nm or 980 nm wavelengths on the prevention of bleaching damage, irrespective of the activation mechanism of the bleaching gel in use.

Effects of incorporation of 2.5 and 5 wt% TiO2 nanotubes on fracture toughness, flexural strength, and microhardness of denture base poly methyl methacrylate (PMMA).

PURPOSE: The aim of this preliminary study was to investigate, for the first time, the effects of addition of titania nanotubes (n-TiO2) to poly methyl methacrylate (PMMA) on mechanical properties of PMMA denture base. MATERIALS AND METHODS: TiO2 nanotubes were prepared using alkaline hydrothermal process. Obtained nanotubes were assessed using FESEM-EDX, XRD, and FT-IR. For 3 experiments of this study (fracture toughness, three-point bending flexural strength, and Vickers microhardness), 135 specimens were prepared according to ISO 20795-1:2013 (n of each experiment=45). For each experiment, PMMA was mixed with 0% (control), 2.5 wt%, and 5 wt% nanotubes. From each TiO2:PMMA ratio, 15 specimens were fabricated for each experiment. Effects of n-TiO2 addition on 3 mechanical properties were assessed using Pearson, ANOVA, and Tukey tests. RESULTS: SEM images of n-TiO2 exhibited the presence of elongated tubular structures. The XRD pattern of synthesized n-TiO2 represented the anatase crystal phase of TiO2. Moderate to very strong significant positive correlations were observed between the concentration of n-TiO2 and each of the 3 physicomechanical properties of PMMA (Pearson's P value ≤.001, correlation coefficient ranging between 0.5 and 0.9). Flexural strength and hardness values of specimens modified with both 2.5 and 5 wt% n-TiO2 were significantly higher than those of control (P≤.001). Fracture toughness of samples reinforced with 5 wt% n-TiO2 (but not those of 2.5% n-TiO2) was higher than control (P=.002). CONCLUSION: Titania nanotubes were successfully introduced for the first time as a means of enhancing the hardness, flexural strength, and fracture toughness of denture base PMMA.

Poly(lactic-co-glycolic acid)(PLGA)/TiO2 nanotube bioactive composite as a novel scaffold for bone tissue engineering: In vitro and in vivo studies.

The aim of this study was to synthesize and characterize novel three-dimensional porous scaffolds made of poly (lactic-co-glycolic acid)/TiO2 nanotube (TNT) composite microspheres for bone tissue engineering applications. The incorporation of TNT greatly increases mechanical properties of PLGA/TNT microsphere-sintered scaffold. The experimental results exhibit that the PLGA/0.5 wt% TNT scaffold sintered at 100 °C for 3 h showed the best mechanical properties and a proper pore structure for tissue engineering. Biodegradation test ascertained that the weight of both PLGA and PLGA/PLGA/0.5 wt% TiO2 nanotube composites slightly reduced during the first 4 weeks following immersion in SBF solution. Moreover, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay and alkaline phosphatase activity (ALP activity) results represent increased cell viability for PLGA/0.5%TNT composite scaffold in comparison to the control group. In vivo studies show the amount of bone formation for PLGA/TNT was approximately twice of pure PLGA. Vivid histologic images of the newly generated bone on the implants further supported our test results. Eventually, a mathematical model showed that both PLGA and PLGA/TNT scaffolds' mechanical properties follow an exponential trend with time as their degradation occurs. By a three-dimensional finite element model, a more monotonous distribution of stress was present in the scaffold due to the presence of TNT with a reduction in maximum stress on bone.

Evaluation of Antimicrobial Properties of Conventional Poly(Methyl Methacrylate) Denture Base Resin Materials Containing Hydrothermally Synthesised Anatase TiO2 Nanotubes against Cariogenic Bacteria and Candida albicans.

The purpose of this study was to investigate the antimicrobial properties of a conventional poly methyl methacrylate (PMMA) modified with hydrothermally synthesised titanium dioxide nanotubes (TNTs). Minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and minimum fungicidal concentrations (MFC) for planktonic cells of the TiO2 nanotubes solution against Lactobacillus acidophilus, Streptococcus mutans and Candida albicans were determined. The powder of conventional acrylic resin was modified using 2.5% and 5% by weight synthesised titanium dioxide (TiO2) nanotubes, and rectangular-shaped specimens (10 mm × 10 mm × 3 mm) were fabricated. The antimicrobial properties of ultraviolet (UV) and non-UV irradiated modified, and non-modified acrylic resins were evaluated using the estimation of planktonic cell count and biofilm formation of the three microorganisms mentioned above. The data were analysed by one-way analysis of variance (ANOVA), followed by a post-hoc Tukey's test at a significance level of 5%. MIC, for Streptococcus. mutans, Lactobacillus. acidophilus, and Candida. albicans, MBC for S. mutans and L. acidophilus and MFC for Candida. albicans were obtained more than 2100 µg/mL. The results of this study indicated a significant reduction in both planktonic cell count and biofilm formation of modified UV-activated acrylic specimens compared with the control group (p = 0.00). According to the results of the current study, it can be concluded that PMMA/TiO2 nanotube composite can be considered as a promising new material for antimicrobial approaches.

Effect of sintering temperature rise from 870 to 920°C on physicomechanical and biological quality of nano-hydroxyapatite: An explorative multi-phase experimental in vitro/vivo study.

Hydroxyapatite (HA) is a proper scaffold for bone repair, however, it is not of excellent mechanical properties. Most previous studies on the effect of temperature increases were in vitro and had assessed merely improvements of HA's physicomechanical quality. This in vitro/vivo study investigated the effect of temperature increases from 870 to 920°C on physicomechanical and biological quality of Nano-HA. Forty experimentally produced HA disks sintered at 870 to 920°C were prepared (n=20×2). Disks were subjected to Vickers microindentation test (1 disk from each group divided into 4 quarters), Fourier transform infrared spectroscopy (1 disk), X-ray diffraction (XRD) [1 disk together with non-sintered HA], field emission scanning electron microscopy (FSEM, 1 disk from each group together with non-sintered HA), cell seeding and SEM assessment (2 disks), MTT assay over 4 different time periods (16 quadrants of 4 disks from each group), 6 one-thirds of 2 disks from each group for immunocytochemical (ICC) assay, and 8 disks from each group [as well as non-sintered HA] for the animal study (implantation in 4 sockets in 8 rabbits [32 specimens], histomorphometry, and computerized tomography) over two time periods. Quantitative data were analyzed statistically (α=0.05). Vickers microhardness increased from 63.7±11.9 in the 870 group to 153.4±104.7 in the 920 group (P=0.057). XRD indicated more regular crystal patterns in sintered groups compared to non-sintered nanoHA. FSEM showed larger crystals in the 920 group compared to 870 and non-sintered nanoHA. Expression of osteocalcin, osteonectin, and RUNX2 genes were more visible in ICC samples of the 920HA group. In MTT, cell numbers increased in all groups significantly (P=0.000), with no between-group differences (P>0.3). In rabbit experiments, the extent of 'newly formed bone' increased significantly over time (two-way ANOVA, P=0.000), reaching 39.5%, 46.4%, and 77.5% in the groups non-sintered HA, 870, and 920, respectively. The 920°C-sintered nanoHA induced the highest bone formation (P=0.000). Increasing the temperature of nanoHA sintering from 870 to 920°C can improve its physicomechanical properties and bone formation potential.

Enhancement of stem cell differentiation to osteogenic lineage on hydroxyapatite-coated hybrid PLGA/gelatin nanofiber scaffolds.

A combination of polymeric materials and bioceramics has recently received a great deal of attention for bone tissue engineering applications. In the present study, hybrid nanofibrous scaffolds were fabricated from PLGA and gelatin via electrospinning and then were coated with hydroxyapatite (HA). They were then characterized and used in stem cell culture studies for the evaluation of their biological behavior and osteogenic differentiation in vitro. This study showed that all PLGA, hybrid PLGA/gelatin and HA-PLGA/gelatin scaffolds were composed of ultrafine fibers with smooth morphology and interconnected pores. The MTT assay confirmed that the scaffolds can support the attachment and proliferation of stem cells. During osteogenic differentiation, bone-related gene expression, ALP activity and biomineralization on HA-PLGA/gelatin scaffolds were higher than those observed on other scaffolds and TCPS. PLGA/gelatin electrospun scaffolds also showed higher values of these markers than TCPS. Taking together, it was shown that nanofibrous structure enhanced osteogenic differentiation of adipose-tissue derived stem cells. Furthermore, surface-coated HA stimulated the effect of nanofibers on the commitment of stem cells toward osteolineage. In conclusion, HA-PLGA/gelatin electrospun scaffolds were demonstrated to have significant potential for bone tissue engineering applications.

Efficacy of the biomaterials 3wt%-nanostrontium-hydroxyapatite-enhanced calcium phosphate cement (nanoSr-CPC) and nanoSr-CPC-incorporated simvastatin-loaded poly(lactic-co-glycolic-acid) microspheres in osteogenesis improvement: An explorative multi-phase experimental in vitro/vivo study.

AIMS: The purpose of this multi-phase explorative in vivo animal/surgical and in vitro multi-test experimental study was to (1) create a 3wt%-nanostrontium hydroxyapatite-enhanced calcium phosphate cement (Sr-HA/CPC) for increasing bone formation and (2) creating a simvastatin-loaded poly(lactic-co-glycolic acid) (SIM-loaded PLGA) microspheres plus CPC composite (SIM-loaded PLGA+nanostrontium-CPC). The third goal was the extensive assessment of multiple in vitro and in vivo characteristics of the above experimental explorative products in vitro and in vivo (animal and surgical studies). METHODS AND RESULTS PERTAINING TO SR-HA/CPC: Physical and chemical properties of the prepared Sr-HA/CPC were evaluated. MTT assay and alkaline phosphatase activities, and radiological and histological examinations of Sr-HA/CPC, CPC and negative control were compared. X-ray diffraction (XRD) indicated that crystallinity of the prepared cement increased by increasing the powder-to-liquid ratio. Incorporation of Sr-HA into CPC increased MTT assay (biocompatibility) and ALP activity (P<0.05). Histomorphometry showed greater bone formation after 4weeks, after implantation of Sr-HA/CPC in 10 rats compared to implantations of CPC or empty defects in the same rats (n=30, ANOVA P<0.05). METHODS AND RESULTS PERTAINING TO SIM-LOADED PLGA MICROSPHERES+NANOSTRONTIUM-CPC COMPOSITE: After SEM assessment, the produced composite of microspheres and enhanced CPC were implanted for 8weeks in 10 rabbits, along with positive and negative controls, enhanced CPC, and enhanced CPC plus SIM (n=50). In the control group, only a small amount of bone had been regenerated (localized at the boundary of the defect); whereas, other groups showed new bone formation within and around the materials. A significant difference was found in the osteogenesis induced by the groups sham control (16.96±1.01), bone materials (32.28±4.03), nanostrontium-CPC (24.84±2.6), nanostrontium-CPC-simvastatin (40.12±3.29), and SIM-loaded PLGA+nanostrontium-CPC (44.8±6.45) (ANOVA P<0.001). All the pairwise comparisons were significant (Tukey P<0.01), except that of nanostrontium-CPC-simvastatin and SIM-loaded PLGA+nanostrontium-CPC. This confirmed the efficacy of the SIM-loaded PLGA+nanostrontium-CPC composite, and its superiority over all materials except SIM-containing nanostrontium-CPC.

Iranian homograft heart valves: assessment of durability and late outcome.

Durability and the rate of complications of homograft heart valves, adjusted for patient-related contributors and surgical techniques, rely mainly on the quality of allografts which in turn are mirrored in the donor characteristics and most importantly recovery and processing procedures. Aimed to assess the quality, a study was conducted to figure out the durability and late outcome following homograft replacement with valved conduits procured by the Iranian Tissue Bank. Retrospectively, the pre-implantation, perioperative and follow-up data of 400 non-consecutive recipients of cryopreserved heart valves (222 pulmonary and 178 aortic) from 2006 to 2015 were collected and analyzed in terms of variables reflecting late outcome including adverse events and durability. In the context of durability, the event of interest was defined as the need for homograft replacement and homograft-related death. The mean follow-up time (SD) of study entrants (male/female ratio, 1.4) was 49.8 (36.3) months. Median age at the time of implantation was 11 years. Total 10-years mortality was 21 % (84/400), including 66.7 % early (30-days mortality: 56/84) and 33.3 % late (28/84). Overall late complication rate was 2 %. Median survival time was 120 months (95 % CI 83.3-156.6). The pulmonary valves appeared to be more durable (P value <0.001) and survival probabilities in small sized grafts were lower (P value 0.008). One-, five-, and ten-year graft survival was 82, 76 and 73 %, respectively. The evidences suggest that the homografts function satisfactory with low rate of late complications; nevertheless, more emphasis should be given to make long-term durability comparable.

The effects of light curing units and environmental temperatures on C = C conversion of commercial and experimental bonding agents.

BACKGROUND AND PURPOSE: Polymerization of bonding agents (BA) is a critical factor in determining the success of bonded restorations. We aimed to assess the effects of two light curing units and two temperatures on the extent of polymerization (EP) of a commercial BA and an experimental BA. METHODS: Forty BA specimens were randomly divided into 8 subgroups of n = 5 to compare the polymerization of two BAs (experimental/Scotchbond) based on the variables: temperature (23/37 °C) and light-curing unit (quartz-tungsten-halogen/light-emitting diode). The EP (%) was measured using differential scanning calorimetry, and analyzed using the t-test, two- and three-way analyses of variance (ANOVA), and the Bonferroni test (α = 0.05). RESULTS: There were significant differences between the EP results between the two BAs (P = 0.012) and due to the different temperatures (P = 0.001), but not between the different light-curing units (P = 0.548). The interaction between BA and temperature was significant (P < 0.001). The other interactions were nonsignificant. CONCLUSIONS: The two light-curing units had similar effects on the EP. The EP values were better when curing was performed at human body temperature.

The effects of dentin bonding agent formulas on their polymerization quality, and together with tooth tissues on their microleakage and shear bond strength: an explorative 3-step experiment.

PURPOSE: Bonding agents (BA) are the crucial weak link of composite restorations. Since the commercial materials' compositions are not disclosed, studies to formulize the optimum ratios of different components are of value. The aim of this study was to find a proper formula of BAs. MATERIALS AND METHODS: This explorative experimental in vitro study was composed of 4 different sets of extensive experiments. A commercial BA and 7 experimental formulas were compared in terms of degree of conversion (5 experimental formulas), shear bond strength, mode of failure, and microleakage (3 experimental formulas). Statistical analyses were performed (α=.05). The DC of selected formula was tested one year later. RESULTS: The two-way ANOVA indicated a significant difference between the shear bond strength (SBS) of two tissues (dentin vs. enamel, P=.0001) in a way that dentinal bonds were weaker. However, there was no difference between the four materials (P=.283). The adhesive mode of failure was predominant in all groups. No differences between the microleakage of the four materials at occlusal (P=.788) or gingival (P=.508) sites were detected (Kruskal-Wallis). The Mann-Whitney U test showed a significant difference between the microleakage of all materials (3 experimental formulas and a commercial material) together at the occlusal site versus the gingival site (P=.041). CONCLUSION: A formula with 62% bisphenol A-glycidyl methacrylate (Bis-GMA), 37% hydroxy ethyl methacrylate (HEMA), 0.3% camphorquinone (CQ), and 0.7% dimethyl-para-toluidine (DMPT) seems a proper formula for mass production. The microleakage and SBS might be respectively higher and lower on dentin compared to enamel.

Polymerization behavior and thermal characteristics of two new composites at five temperatures: refrigeration to preheating.

PURPOSE: Heat of composite polymerization (HP) indicates setting efficacy and temperature increase of composite in clinical procedures. The purpose of this in vitro experimental study was to evaluate the effects of 5 temperatures on HP of two new composites. MATERIALS AND METHODS: From each material (Core Max II [CM] and King Dental [KD]), 5 groups of 5 specimens each were prepared and their total HPs (J/gr) were measured and recorded, at one of the constant temperatures 0℃, 15℃, 23℃, 37℃ and 60℃ (2 × 5 × 5 specimens) using a differential scanning calorimetry (DSC) analyzer. The data were analyzed using a two-way ANOVA, a Tukey's test, an independent-samples t-test, and a linear regression analysis (α=0.05). RESULTS: No polymerization reactions occurred at 0℃; then this temperature was excluded from statistical analyses. The mean HP of the remaining 20 KD specimens was 20.5 ± 14.9 J/gr, while it was 40.7 ± 12.9 J/gr for CM. The independent-samples t-test showed that there were significant differences between the HP of the two materials at the temperatures 15℃ (P=.0001), 23℃ (P=.0163), 37℃ (P=.0039), and 60℃ (P=.0106). Linear regression analysis showed statistically significant correlations between environment temperatures and HP of CM (R(2)=0.777). CONCLUSION: Using CM is advantageous over conventional composite because of its better polymerization capacity. However due to its high HP, further studies should assess its temperature increase in vivo. Preheating KD is recommended. Refrigerating composites can negatively affect their polymerization potential.

Evaluating the In-vitro Antibacterial Effect of Iranian Propolis on Oral Microorganisms.

Propolis has traditionally been used in curing infections and healing wounds and burns. Current researches have shown that propolis has antibacterial, antifungal and antiviral actions however, the pharmacological activity of propolis is highly variable depending on its geographic origin. There have been few studies on the effects of Iranian propolis on the oral microorganisms. In this in-vitro study, the antimicrobial activity of the ethanolic and water extracts of the Iranian propolis (10%, w/v) from north-east area of Tehran was evaluated. Susceptibility of the oral strains tested (Streptococcus mutans ATCC 35668; Streptococcus salivarius ATCC 9222; Staphylococcus aureus ATCC 25923; Enterococcus faecalis ATCC 9854 and Lactobacillus casei ATCC 39392) was evaluated using the agar diffusion method at a concentration of 20 mg/mL of propolis and the zones of growth inhibition were measured. Antibacterial activity was determined by using minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) at different concentrations of propolis. The ethanolic extract showed bacteriostatic and bactericidal activity against all the strains, with MIC and MBC ranges of 250-500 µg/mL. The MIC concentration of the water extract was 500 µg/mL against S. mutans and E. faecalis. The water extract showed bactericidal activity only against S. mutans (20 mg/mL). These results indicate that the ethanolic extract is probably more useful in the control of oral biofilms and subsequent dental caries development. However, to determine the consequence of the ethanolic extract of Iranian propolis on the oral mucosa, in-vivo studies of its possible effects are needed.