Hydrophilic dyes as photosensitizers for photopolymerization of dental adhesives.

OBJECTIVES: This study explored hydrophilic dyes as photosensitizers for application in dental adhesives. The goal was to identify dyes that enhance the degree of conversion (DC) of the hydrophilic-rich phase without impairing polymerization of the hydrophobic-rich phase. METHODS: Properties that were investigated included the molar extinction coefficient at 480 nm, relative normalized photon absorption efficiency (PAE), rate of polymerization and degree of conversion (DC). The following hydrophilic dyes: Bromophenol blue sodium salt, Rosebengal sodium salt, Erythrosin B, New Fuchsin and Victoria blue B were identified as suitable photosensitizers. RESULTS: In this study it was observed that dyes such as Bromophenol blue sodium salt, New Fuchsin, Victoria blue B and Rosebengal sodium salt were suitable candidates for dental adhesive photopolymerization, leading to substantial degree of conversion to both the hydrophilic-rich phase and the hydrophobic-rich phase. CONCLUSIONS: In addition to the ability of the photosensitizer to absorb light in the visible range and transition to an excited state as a result of the absorbed energy, other factors such as the efficiency of the photosensitizer/light curing unit (LCU) combination, stability/efficiency of the excited state of the photosensitizer and/or initiating reactive species play an important role in the photopolymerization of the dental adhesive.

Computer-aided Molecular Design of Water Compatible Visible Light Photosensitizers for Dental Adhesive.

Dental adhesive resin undergoes phase separation during its infiltration through the wet demineralized dentin and it has been observed previously that the hydrophilic-rich phase is a vulnerable region for failure due to the lack of photo-polymerization and crosslinking density. The lack of photo-polymerization is mostly due to the partitioning of photo-initiators in low concentrations within this phase. Here, a computational approach has been employed to design candidate water compatible visible light photosensitizers which could improve the photo-polymerization of the hydrophilic-rich phase. This study is an extension of our previous work. QSPRs were developed for properties related to the photo-polymerization reaction of the adhesive monomers and hydrophilicity of the photosensitizer using connectivity indices as descriptors. QSPRs and structural constraints were formulated into an optimization problem which was solved stochastically via Tabu Search. Four candidate photosensitizer molecules have been proposed here which have the iminium ion as a common feature.

Effect of Partition of Photo-initiator Components and Addition of Iodonium Salt on the Photopolymerization of Phase-Separated Dental Adhesive.

The polymerization kinetics of physically separated hydrophobic- and hydrophilic-rich phases of a model dental adhesive have been investigated. The two phases were prepared from neat resin containing 2-hydroxyethyl methacrylate (HEMA) and bisphenol A glycerolate dimethacrylate (BisGMA) in the ratio of 45:55 (wt/wt). Neat resins containing various combinations of popular photo-initiating compounds, e.g., camphoquinone (CQ), ethyl 4-(dimethylamino)benzoate (EDMAB), 2-(dimethylamino)ethyl methacrylate (DMAEMA) and diphenyliodonium hexafluorophosphate (DPIHP) were prepared. To obtain the two phases 33 wt% of deuterium oxide (D2O) was added to the neat resins. This amount of D2O exceeded the miscibility limit for the resins. The concentration of each component of the photo-initiating system in the two phases was quantified by HPLC. When combined with CQ, DMAEMA is less efficient as a co-initiator compared to EDMAB. The addition of DPIHP as the third component into either CQ/EDMAB or CQ/DMAEMA photo-initiating systems leads to comparable performance in both the hydrophobic- and hydrophilic-rich phases. The addition of the iodonium salt significantly improved the photopolymerization of the hydrophilic-rich phase; the hydrophilic-rich phase exhibited extremely poor polymerization when the iodonium salt was not included in the formulation. The partition concentration of EDMAB in the hydrophilic-rich phase was significantly lower than that of DMAEMA or DPIHP. This study indicates the need for a combination of hydrophobic/hydrophilic photosensitizer and addition of iodonium salt to improve polymerization within the hydrophilic-rich phase of the dental adhesive.

Impact of light intensity on the polymerization kinetics and network structure of model hydrophobic and hydrophilic methacrylate based dental adhesive resin.

The impact of light intensity on the degree of conversion (DC), rate of polymerization and network structure was investigated for hydrophobic and hydrophilic dental adhesive resins. Two and three component photoinitiating (PI) systems were used in this study. Low light intensities had a negative impact on the polymerization efficiency for the hydrophilic resin with 2 component PI system. Incorporation of iodonium salt in the hydrophilic resin significantly improved the polymerization efficiency of the HEMA/BisGMA system and led to a substantial DC, even at low light intensities. The results suggested that shorter polymer chains were formed in the presence of iodonium salt. It appears that there is little or no impact of light intensity on the polymer structure of the 2 component PI system. Light intensity has subtle impact on the polymer structure of the 3 component PI system. In the case of the hydrophobic resin, the polymer is so highly cross-linked that the presence of shorter chains for the 3 component PI system does not cause a decrease in the glass transition temperature (Tg ) when compared to the 2 component PI system. For the hydrophilic resin, the presence of shorter polymer chains in the 3 component PI system reduces the Tg when compared with the corresponding 2 component PI system. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1666-1678, 2016.

Albumin-based micro-composite drug carriers with dual chemo-agents for targeted breast cancer treatment.

Albumin-based drug-carrying micro-composite spheres were fabricated and studied to evaluate their potentials for breast cancer treatment. Magnetic nanoparticles and albumin were incorporated within poly(D l-lactide-co-glycolide) microspheres to increase accumulation of the microspheres at the target site. Two chemotherapeutics, cyclophosphamide and 5-fluorouracil, were encapsulated into the microspheres. The drug-release study revealed an initial burst of drug and then sustained release by diffusion. A Fourier transform infrared spectroscopy study confirmed the presence of all components of the drug delivery system. An in vitro study using fibroblast cells (3T3) and breast cancer cells (MDA-486) exhibited an effective cytotoxicity behavior when exposed to the drug delivery system in a dose- and time-dependent manner. The therapeutic influence of the drug delivery system was evaluated in vivo using a nude mouse breast cancer model. A continuous decrease in tumor size was observed in groups treated with microspheres containing the chemotherapeutics, whereas mice treated with direct chemotherapy without drug delivery system showed less efficacy and suggested tumor relapse after cessation of treatment. The enhanced therapeutic influence of the drug delivery system may be attributed to the increased uptake of the microspheres by malignant cells due to the presence of albumin and magnetic force. The bioavailability of chemotherapeutics at the target site was further increased due to the sustained release of the drugs by diffusion following the burst release. Continuous investigations will optimize the size of the drug delivery system and portions of the target driving-force components (magnetic nanoparticles and albumin) in the drug delivery system to maximize its therapeutic efficacy and minimize potential long-term side effects.

Polymerization- and solvent-induced phase separation in hydrophilic-rich dentin adhesive mimic.

Current dental resin undergoes phase separation into hydrophobic-rich and hydrophilic-rich phases during infiltration of the over-wet demineralized collagen matrix. Such phase separation undermines the integrity and durability of the bond at the composite/tooth interface. This study marks the first time that the polymerization kinetics of model hydrophilic-rich phase of dental adhesive has been determined. Samples were prepared by adding varying water content to neat resins made from 95 and 99 wt.% hydroxyethylmethacrylate and 5 and 1 wt.% (2,2-bis[4-(2-hydroxy-3-methacryloxypropoxy)phenyl1]-propane prior to light curing. Viscosity of the formulations decreased with increased water content. The photopolymerization kinetics study was carried out with a time-resolved Fourier transform infrared spectrometer. All of the samples exhibited two-stage polymerization behavior which has not been reported previously for dental resin formulation. The lowest secondary rate maxima were observed for water contents of 10-30 wt.%. Differential scanning calorimetry (DSC) showed two glass transition temperatures for the hydrophilic-rich phase of dental adhesive. The DSC results indicate that the heterogeneity within the final polymer structure decreased with increasing water content. The results suggest a reaction mechanism involving both polymerization-induced phase separation and solvent-induced phase separation for the model hydrophilic-rich phase of dental resin.

Multivariate analysis of attenuated total reflection Fourier transform infrared (ATR FT-IR) spectroscopic data to confirm phase partitioning in methacrylate-based dentin adhesive.

Water is ubiquitous in the mouths of healthy individuals and is a major interfering factor in the development of a durable seal between the tooth and composite restoration. Water leads to the formation of a variety of defects in dentin adhesives; these defects undermine the tooth-composite bond. Our group recently analyzed phase partitioning of dentin adhesives using high-performance liquid chromatography (HPLC). The concentration measurements provided by HPLC offered a more thorough representation of current adhesive performance and elucidated directions to be taken for further improvement. The sample preparation and instrument analysis using HPLC are, however, time-consuming and labor-intensive. The objective of this work was to develop a methodology for rapid, reliable, and accurate quantitative analysis of near-equilibrium phase partitioning in adhesives exposed to conditions simulating the wet oral environment. Analysis by Fourier transform infrared (FT-IR) spectroscopy in combination with multivariate statistical methods, including partial least squares (PLS) regression and principal component regression (PCR), were used for multivariate calibration to quantify the compositions in separated phases. Excellent predictions were achieved when either the hydrophobic-rich phase or the hydrophilic-rich phase mixtures were analyzed. These results indicate that FT-IR spectroscopy has excellent potential as a rapid method of detection and quantification of dentin adhesives that experience phase separation under conditions that simulate the wet oral environment.