Time Frame Analysis of Potassium Nitrate and Hydrogen Peroxide Diffusion into the Pulp Chamber.

OBJECTIVES: The primary objective of this study was to evaluate the effect of an innovative double-layer, single-application desensitizing/whitening technique of potassium nitrate (PN) and hydrogen peroxide (HP) diffusion at different time points. METHODS AND MATERIALS: Specimens were prepared from extracted caries-free human molars (n=90). Teeth were randomly assigned into four groups: Group A (HP CTRL) treated with 25% HP for 45 minutes, group B (PN CTRL) received a single-layer treatment of 5% PN for 45 minutes, group C received the double-layer treatment of 5% PN and 25% HP for 45 minutes, and group D received a 3% PN incorporated in a 40% HP gel for 45 minutes. PN and HP concentrations were measured at 5, 15, 30, and 45 minutes using standard chemical kits. Group comparisons were made using a repeated measures analysis of variance (ANOVA) test. Pairwise tests for differences in diffusion were done, using the Tukey adjustment of p values for multiple comparisons. A significance level of 5% was used. RESULTS: Group A showed no significant difference in HP diffusion rates between the 5- and 15-minute, 15- and 30-minute, or 30- and 45-minute time points; group D showed a similar trend; however, group C differed significantly at the 5-and 15-minute time points (p=0.0004), at the 15-and 30-minute time points (p=0.0026), and the 30- and 45-minute time points (p=0.0014). For PN diffusion, groups B and C had significantly different levels at the 15-, 30-, and 45-minute time points (p=0.0005, p=0.0002, and p<0.0001, respectively); and at the 15-, 30-, and 45-minute time points, groups D and C had significantly different PN diffusion (p=0.0327, p=0.0004, and p< 0.0001, respectively). Group C had significantly different PN diffusion at the 5- and 15-minute time points (p=0.0004), the 15- and 30-minute time points (p=0.0026), and at the 30- and 45-minute time points (p=0.0014). CONCLUSION: The double-layer technique showed superior diffusion of PN into the pulp chamber and did not affect the diffusion of HP when compared to other techniques. The double-layer technique may be suggested as an alternative tooth-whitening treatment to minimize tooth sensitivity.

Antibiotic Delivery Strategies to Treat Skin Infections When Innate Antimicrobial Defense Fails.

The epidermal skin barrier protects the body from a host of daily challenges, providing protection against mechanical insults and the absorption of chemicals and xenobiotics. In addition to the physical barrier, the epidermis also presents an innate defense against microbial overgrowth. This is achieved through the presence of a diverse collection of microorganisms on the skin (the "microbiota") that maintain a delicate balance with the host and play a significant role in overall human health. When the skin is wounded, the local tissue with a compromised barrier can become colonized and ultimately infected if bacterial growth overcomes the host response. Wound infections present an immense burden in healthcare costs and decreased quality of life for patients, and treatment becomes increasingly important because of the negative impact that infection has on slowing the rate of wound healing. In this review, we discuss specific challenges of treating wound infections and the advances in drug delivery platforms and formulations that are under development to improve topical delivery of antimicrobial treatments.

Surfactant-induced spreading of nanoparticles is inhibited on mucus mimetic surfaces that model native lung conditions.

We investigated the ability of surfactant-induced spreading to promote nanoparticle distribution on model mucus hydrogels. The hydrogels were formulated with viscoelastic properties and surface tensions that match those of native lung mucus. Nanoparticle-containing droplets with or without surfactant were deposited on the mucus surface and spreading patterns were monitored by time-course fluorescence imaging. Overall, surfactant-induced spreading of nanoparticles required an appropriate balance between Marangoni forces and viscoelastic subphase resistance. Spreading was enhanced on bare gels by increasing the concentration of surfactant in the droplets or reducing the viscoelastic properties of the subphase. However, with a pre-existing film of pulmonary surfactant on the mucus surface, spreading was dramatically inhibited as the surface tension gradient between the droplets and the surrounding subphase decreased. A complete lack of spreading was observed at surface tensions that matched those in the tracheobronchial region of the lungs, even with full-concentration Infasurf. These studies demonstrate that the magnitude of spreading on lung mucus-like surfaces is limited by native mucosal properties.

Dry powder aerosols to co-deliver antibiotics and nutrient dispersion compounds for enhanced bacterial biofilm eradication.

The purpose of this study was to formulate a dry powder for inhalation containing a combination treatment for eradication of Pseudomonas aeruginosa bacterial biofilms. Dry powders containing an antibiotic (ciprofloxacin hydrochloride, CH) and nutrient dispersion compound (glutamic acid, GA) at a ratio determined to eliminate the biofilms were generated by spray drying. Leucine was added to the spray dried formulation to aid powder flowability. A central composite design of experiments was performed to determine the effects of solution and processing parameters on powder yield and aerodynamic properties. Combinations of CH and GA eradicated bacterial biofilms at lower antibiotic concentrations compared to CH alone. Spray dried powders were produced with yields up to 43% and mass mean aerodynamic diameters (MMAD) in the respirable range. Powder yield was primarily affected by variables that determine cyclone efficiency, i.e. atomizer and solution flow rates and solution concentration; while MMAD was mainly determined by solution concentration. Fine particle fractions (FPF)<4.46µm and <2.82µm of the powders ranged from 56 to 70% and 35 to 46%, respectively. This study demonstrates that dry powder aerosols containing high concentrations of a combination treatment effective against P. aeruginosa biofilms could be developed with high yield, aerodynamic properties appropriate for inhalation, and no loss of potency.

Spectrophotometric Evaluation of Potassium Nitrate Penetration Into the Pulp Cavity.

OBJECTIVES: The aim of this study was to evaluate the penetration level of potassium nitrate-containing desensitizers or whitening materials into the pulp cavity with regard to the concentration and viscosity of the formulation. METHODS AND MATERIALS: Fifty extracted human molar teeth were prepared and randomized into five groups of 10 specimens each. The control received a 30-minute treatment without any treatment material; the other four groups corresponded to treatment with DayWhite, a 14% hydrogen peroxide whitening material containing potassium nitrate; PreviDent 5000 Sensitive, a desensitizing toothpaste; Relief ACP, a desensitizing gel; or UltraEZ, a desensitizing gel. Potassium nitrate penetration levels were measured spectrophotometrically based on the Griess assay method. Treatment materials were measured for viscosity as a function of shear rate through the use of a cone-and-plate rheometer. RESULTS: Nitrate penetration levels were significantly different among the five groups (p<0.0001, Kruskal-Wallis test). After adjustment for multiple comparisons using an overall 0.05 level of type I error, the distribution of nitrate penetration values was found to differ significantly among all groups with the exception of DayWhite (median: 10.72 µM) and UltraEZ (median: 9.22 µM), which differed significantly from other groups but not from each other. The highest levels of nitrate penetration value were observed for PreviDent (median: 27.61 µM) followed by Relief ACP (median: 19.64 µM). The lowest penetration level was observed for the control group (median: 3.41 µM). Stable end-point viscosities of 11.43 ± 0.67 Pa/s, 1.33 ± 0.06 Pa/s, 0.85 ± 0.09 Pa/s, and 0.40 ± 0.01 Pa/s were observed for UltraEZ, ReliefACP, DayWhite, and PreviDent, respectively. CONCLUSION: Potassium nitrate included in different formulations can penetrate the enamel and dentin within 30 minutes. The level of potassium nitrate penetration is influenced by concentration and may also be partly affected by the viscosity of the material as well as other constituents of proprietary preparations.

Synthetic tracheal mucus with native rheological and surface tension properties.

In this study, the development of a model tracheal mucus with chemical composition and physical properties (bulk viscoelasticity and surface tension) matched to that of native tracheal mucus is described. The mucus mimetics (MMs) were formulated using components that are abundant in tracheal mucus (glycoproteins, proteins, lipids, ions, and water) at concentrations similar to those found natively. Pure solutions were unable to achieve the gel behavior observed with native mucus. The addition of a bifunctional cross-linking agent enabled control over the viscoelastic properties of the MMs by tailoring the concentration of the cross-linking agent and the duration of cross-linking. Three MM formulations with different bulk viscoelastic properties, all within the normal range for nondiseased tracheal mucus, were chosen for investigation of surfactant spreading at the air-mimetic interface. Surfactant spread quickly and completely on the least viscoelastic mimetic surface, enabling the surface tension of the mimetic to be lowered to match native tracheal mucus. However, surfactant spreading on the more viscoelastic mimetics was hindered, suggesting that the bulk properties of the mimetics dictate the range of surface properties that can be achieved.

Inhaled large porous particles of capreomycin for treatment of tuberculosis in a guinea pig model.

Capreomycin is used for the treatment of multidrug-resistant tuberculosis (MDR-TB), but it is limited therapeutically by its severe side effects. The objectives of the present studies were (i) to design low-density porous capreomycin sulfate particles for efficient pulmonary delivery to improve local and systemic drug bioavailability and capacity to reduce the bacillary load in the lungs in a manner similar to that achieved with intramuscular injections; (ii) to determine pharmacokinetic parameters after pulmonary administration of these capreomycin particles; and (iii) to evaluate the efficacy of these particles in treating animals in a small-aerosol-inoculum guinea pig model of TB. Capreomycin particles were manufactured by spray drying and characterized in terms of size and drug content. Pharmacokinetic parameters were determined by noncompartmental methods with healthy guinea pigs after administration of capreomycin particles by insufflation. The efficacy of the particles was evaluated by histopathological analysis and in terms of wet organ weight and bacterial burden in TB-infected animals. Lungs of animals receiving a 14.5-mg/kg dose of capreomycin particles showed significantly lower wet weights and smaller bacterial burdens than those of animals receiving any other treatment. These results were supported by histopathological analysis. The feasibility of inhaling capreomycin in a novel powder form, with the ultimate objective of the treatment of MDR-TB, is demonstrated by pharmacokinetic and pharmacodynamic studies with guinea pigs. If applied to humans with MDR-TB, such a therapeutic approach might simplify drug delivery by eliminating injections and might reduce adverse effects through lowering the dose.

Drug absorption by the respiratory mucosa: cell culture models and particulate drug carriers.

The inhalation route is of increasing interest for both local and systemic drug delivery, including macromolecular biopharmaceuticals, such as peptides, proteins, and gene therapeutics. In addition to appropriate aerosolization for deposition in relevant areas of the respiratory tract, therapeutic molecules may require an advanced carrier system for safe and efficient delivery to their target. Two approaches to obtain novel carrier systems for pulmonary drug delivery are large porous microparticles with a low aerodynamic diameter and lectin-functionalized liposomes. Epithelial cells of alveolar or bronchial origin, obtained either from patient material or from established cell lines, can be grown on permeable filter supports, resulting in polarized monolayers with functional intercellular junctions. With such in vitro models, transport of drugs into pulmonary epithelial cells and/or across the air-blood barrier, as well as the effect and efficacy of novel drug carrier systems can be systematically studied.