Succinyl-ß-cyclodextrin: Influence of the substitution degree on albendazole inclusion complexes probed by NMR.

Succinyl-ß-CD derivatives were obtained by green synthesis with degrees of substitution (DS) 1.3 and 2.9. The spray-drying technique was used to obtain albendazole (ABZ):succinyl-ß-CD inclusion complexes. Phase solubility diagrams indicated that both succinyl-ß-CD derivatives formed 1:1 molar ratio ABZ complexes, but the complex with DS 2.9 has a lower formation constant. The presence of stable inclusion complexes in aqueous solution was confirmed by NMR. For both complexes the aromatic moiety is encapsulated into the host cavity. In the solid-state, 13C and 15N NMR spectral differences between ABZ and ABZ included in spray-dried systems showed that strong structural changes occurred in the systems. At least two different ABZ amorphous species were identified based on DS. ABZ species were stable over more than six months based on spectral data. Finally, the influence of DS in the number and type of the inclusion complexes was elucidated.

Improving sustained drug delivery from ophthalmic lens materials through the control of temperature and time of loading.

Although the possibility of using drug-loaded ophthalmic lens to promote sustained drug release has been thoroughly pursued, there are still problems to be solved associated to the different alternatives. In this work, we went back to the traditional method of drug loading by soaking in the drug solution and tried to optimize the release profiles by changing the temperature and the time of loading. Two materials commercially available under the names of CI26Y and Definitive 50 were chosen. CI26Y is used for intraocular lenses (IOLs) and Definitive 50 for soft contact lenses (SCLs). Three drugs were tested: an antibiotic, moxifloxacin, and two anti-inflammatories, diclofenac and ketorolac. Sustained drug release from CI26Y disks for, at least 15 days, was obtained for moxifloxacin and diclofenac increasing the loading temperature up to 60 °C or extending the loading time till two months. The sustained release of ketorolac was limited to about 8 days. In contrast, drug release from Definitive 50 disks could not be improved by changing the loading conditions. An attempt to interpret the impact of the loading conditions on the drug release behavior was done using solid-state NMR and differential scanning calorimetry. These studies suggested the establishment of reversible, endothermic interactions between CI26Y and the drugs, moxifloxacin and diclofenac. The loading temperature had a slight effect on the mechanical and optical properties of drug loaded CI26Y samples, which still kept adequate properties to be used as IOL materials. The in vivo efficacy of CI26Y samples, drug loaded at 60 °C for two weeks, was predicted using a simplified mathematical model to estimate the drug concentration in the aqueous humor. The estimated concentrations were found to comply with the therapeutic needs, at least, for moxifloxacin and diclofenac.

The effect of albumin and cholesterol on the biotribological behavior of hydrogels for contact lenses.

The irritation/discomfort associated with the use of contact lenses (CLs) is often related to the eyelid-lens friction. Although the use of such devices is widespread, the information about the influence of the lacrimal fluid biomolecules on the tribological behavior of the CLs hydrogels is scarce. In this work, we investigated the effect of the presence of albumin and cholesterol in the lubricant medium, on the frictional response of two model hydrogels for CLs: a hydroxyethylmethacrylate based hydrogel, HEMA/PVP, and a silicone based one, TRIS/NVP/HEMA. Tribological experiments were done in a nanotribometer, in water and in the presence of solutions of those biomolecules. It was observed a significant increase of the friction coefficient (µ) for HEMA/PVP when the lubricant contains cholesterol, and for TRIS/NVP/HEMA when it contains albumin. Solid-state NMR and DSC analysis revealed that HEMA/PVP hydrated in cholesterol solution has a lower amount of free and loosely bound water than the hydrogel hydrated in water. Therefore, a smaller amount of water shall be released into the contact region during the friction tests with cholesterol solution, leading to a thinner film in the contact zone, and consequently to a higher µ. Concerning TRIS/NVP/HEMA, QCM-D studies showed that this hydrogel adsorbs less albumin than HEMA/PVP and that the formed film is more rigid, which can explain the increase of µ. The obtained results contribute to understand the influence of lacrimal fluid composition on the tribological behavior of CLs materials, being relevant for the selection and optimization of these devices. STATEMENT OF SIGNIFICANCE: Understanding the tribological behavior of contact lenses (CLs) materials in contact with the lacrimal fluid and the role of its components is of major importance to optimize the comfort and overall success of these devices. Nevertheless, the available information on this subject in the literature is scarce. In this work, the effect of albumin and cholesterol (two of the main components of the lacrimal fluid) on the frictional response of distinct types of hydrogels suitable for CLs, is compared, for the first time. Significant differences were observed with the two molecules, depending on the material, stressing the need to further study this issue to understand, predict and optimize the in vivo performance of CLs.

Towards a controlled photopolymerization of dental dimethacrylate monomers: EPR studies on effects of dilution, filler loading, storage and aging.

Electron paramagnetic resonance (EPR) was used to study the kinetics of methacrylate radical formation in the monomer mixture 2,2-bis [4-(2-hydroxy-3-methacryloxyprop-1-oxy) phenyl] propane (Bis-GMA)/triethylene glycol dimethacrylate (TEGDMA), in the presence of a photo-initiator system (camphorquinone, CQ/N,N-dimethyl-p-toluidine, DET). Curing-time dependences on the filler (0-40 wt%) and TEGDMA content (15-90 wt%) were evaluated; the influence of irradiation protocol, uncured sample storage time and aging of cured systems were also studied. EPR enabled observing at least two different kinetic regimes during polymerization. The final radical concentration decreased both with Bis-GMA and filler content. However, a reverse trend was obtained when the relative photo-initiator concentrations were considered. Filler also showed a significant effect on the radical life-time reduction. Irradiation protocol and storage time of uncured matrices showed to affect the free radical concentration. The observed changes on the EPR signal lineshape with post-curing time suggests that the distribution of CH(2) conformations also changes with time.

Effect of treated filler loading on the photopolymerization inhibition and shrinkage of a dimethacrylate matrix.

This study shows how treated filler loading influences the photopolymerization of a dimethacrylate comonomer mixture, regarding, in particular, shrinkage and inhibition under atmospheric oxygen, present in oral environment. Bis-GMA/TEGDMA (75/25 wt.%) resins were loaded with hybrid filler (Ba aluminosilicate glass and pyrogenic silica), treated with gamma-methacryloxy(propyl)trimethoxysilane, at 0-50 wt.% and light cured over a total of 30 s (45 mW/cm2). Degree of double-bond conversion (DC), obtained using FTIR, decreased with filler content. 1H MAS spectra (293-340 K) and STRAFI images (293 K) were obtained as a function of irradiation time and filler concentration. 1H signals of unreacted methacrylate groups were more intense for higher loaded resins and resonances from -CH2SiO2(OH) (T2) and -CH2SiO3- (T3) units, also observed by 29Si NMR, were resolved and suggest the presence of T2-resin bonds. 1D images show a reduction on polymerization contraction and reaction inhibition at the composite resin surface with filler loading. 2D resin images present a highly mobile surface layer, hence with lower DC.

The first proton NMR imaging of ice: stray-field imaging and relaxation studies.

A proton magnetic resonance image of ice was observed with the stray-field (STRAFI) technique. A preliminary study of proton relaxation times was performed in water and ice, at different temperatures. For example, a value of 3.5 micros for the spin-spin relaxation time, T(2), was found in ice at 258 K. Such a short T(2) value leads to significant signal loss, as compared to liquid water, and to a shortening of the STRAFI echo-trains. In particular, a STRAFI signal for protons in ice could be observed only at echo times as short as 15 and 25 micros, for RF pulse durations corresponding to 90 degrees and 50 degrees magnetisation tip angles, respectively. This behaviour is in contrast with that of deuteriated water. Imaging ice, as shown here, opens new prospects in studies involving environmental and materials science, for example.

Polymerization efficacy of simplified adhesive systems studied by NMR and MRI techniques.

OBJECTIVE: To ascertain the efficacy of polymerization of self-etching dental adhesives in different solvent evaporation conditions. MATERIAL AND METHODS: Four self-etching adhesive systems were studied. Two of them are classified as mild two-step self-etching adhesives (Clearfil SE Bond, Protect Bond) and the other two are strong one-step systems (Xeno III, ADP-Prompt-L-Pop). The influence of temperature and duration of the air-drying period on photo-polymerization was followed by: gravimetry, (1)H solid-state NMR spectroscopy and stray-field MRI. The evolution of proton magnetization with irradiation time was recorded and correlated with volumetric polymerization shrinkage and extent of reaction; evaporation and hardening effects were identified. RESULTS: Main variables determining water-solvent evaporation of the tested adhesives are: (1) water/HEMA relative concentration, (2) presence of photoinitiator compounds in the primer (SEB) and (3) presence of ethanol (XENO). SEB shows the highest extent of photo-polymerization of the tested adhesives. The lowest volumetric contraction was obtained for APLP and XENO and the attempt to remove the solvents did not increase the extent of polymerization significantly. CONCLUSIONS: Temperature increase following photo-polymerization reaction is dominant towards the effect of the drying step for solvent evaporation in self-etching systems. Attempts to remove the solvents did not increase the extent of polymerization, so other problems are impairing the polymerization of one-step adhesives. CLINICAL SIGNIFICANCE: The use of tested one-step adhesives is discouraged as the attained low extent of polymerization may lead to low bond strength, high susceptibility to degradation and also will favor a continuing etching effect on the underlying dentin.

T1-weighting of Hahn echo-trains in the stray-field for deuterium: prospects for imaging using long echo-train summation.

Hahn-echoes have been observed in stray-field gradients of 37.5 T/m and 74.5 T/m for deuterium in heavy water in a number of forms: liquid, ice, and coordinated in solid copper sulfate and silica gel. In the diamagnetic samples, the application of many pulses (> 1000 or more) in long pulse-trains produced many sustained echoes. This lengthening of T(echo) is caused by T1-weighting of the components of the Hahn echo (even in the absence of spin-locking). In contrast, for the paramagnetic complex, the shortening of T1 greatly reduces T(echo) and only few echoes are obtained. A new protocol for stray field imaging is suggested when T1 is long: long echo-train summation (LETS). The observed magnetisation is much greater for heavy ice than for heavy water because the line-width, and hence the thickness of the excited slice, is greater.