Two strategies to enhance ungual drug permeation from UV-cured films: Incomplete polymerisation to increase drug release and incorporation of chemical enhancers.

UV-curable gels, which polymerise into long-lasting films upon exposure to UVA, have been identified as potential topical drug carriers for the treatment of nail diseases. Limitations of such films include incomplete drug release and low ungual drug permeation. The aim of the work herein was therefore to investigate two strategies, namely: (1) increasing drug release from the film, and (2) increasing nailplate permeability, with the ultimate goal of enhancing ungual drug permeation. To increase drug release via Strategy 1, a UV-LED lamp (whose emitted light was suboptimal for gel polymerisation) was used, and it was hypothesised that such a lamp would result in films that are less polymerised/cross-linked and where the drugs are less 'trapped'. Indeed, the suboptimal lamp influenced polymerisation, such that the films were thinner, had lower glass transition temperatures and enabled a slightly greater (by 15%) drug release of one of the two drugs tested. However, the greater drug release had only a modest impact on ungual drug permeation. To evaluate Strategy 2, i.e. increase nailplate permeability, chemical ungual enhancers, 2-mercaptoethanol (ME), 2-methyl pyrrolidone (NMP), PEG 200 and water were incorporated within the UV-cured films. These chemicals caused increased ungual drug permeation, with ME showing the greatest (by 140%), and water showing the least (by 20%) increase in the amount of drug permeated by day 30. Surprisingly, these chemicals also caused increased drug release from the films, with ME once again having the greatest effect (by 51%) and water the least effect (by 12%). It seems that these chemicals were increasing ungual drug permeation via their influence on drug release (i.e. via their impact on the film) as well as via their influence on the nail itself. We conclude that, of the two strategies tested, the second strategy proved to be more successful at enhancing ungual drug permeation.

Delayed photo-activation and addition of thio-urethane: Impact on polymerization kinetics and stress of dual-cured resin cements.

OBJECTIVE: 1) to determine the moment during the redox polymerization reaction of dual cure cements at which to photo-activate the material in order to reduce the polymerization stress, and 2) to evaluate possible synergistic effects between adding chain transfer agents and delayed photo-activation. METHODS: The two pastes of an experimental dual-cure material were mixed, and the polymerization kinetics of the redox phase was followed. The moment when the material reached its maximum rate of redox polymerization (MRRP) of cement was determined. The degree of conversion (DC) and maximum rates of polymerization (Rpmax) were assessed for materials where: the photoactivation immediately followed material mixing, at MRRP, 1min before and 1min after MRRP. Thio-urethane (TU) additives were synthesized and added to the cement (20% wt), which was then cured under the same conditions. The polymerization kinetics was evaluated for both cements photo-activated immediately or at MRRP, followed by measurements of polymerization stress, flexural strength (FS) and elastic modulus (EM). Knoop hardness was measured before and after ethanol storage. RESULTS: Photo-activating the cement at or after MRRP reduced the Rpmax and the polymerization stress. Addition of TU promoted additional and more significant reduction, while not affecting the Rpmax. Greater hardness loss was observed for cements with TU, but the final hardness was similar for all experimental conditions. Addition of TU slightly reduced the EM and did not affect the FS. CONCLUSION: Delayed photo-activation and addition of TU significantly reduce the polymerization stress of dual-cured cements.

UV-curable gel formulations: Potential drug carriers for the topical treatment of nail diseases.

Nail diseases are common, cause significant distress and treatments are far from successful. Our aim was to investigate the potential of UV-curable gels - currently used as cosmetics - as topical drug carriers for their treatment. These formulations have a long residence on the nail, which is expected to increase patient compliance and the success of topical therapy. The gels are composed of the diurethane dimethacrylate, ethyl methacrylate, 2-hydroxy-2-methylpropiophenone, an antifungal drug (amorolfine HCl or terbinafine HCl) and an organic liquid (ethanol or NMP) as drug solvent. Following its application to a substrate and exposure to a UVA lamp for 2 min, the gel polymerises and forms a smooth, glossy and amorphous film, with negligible levels of residual monomers. No drug-polymer interactions were found and drug loading did not affect the film's properties, such as thickness, crystallinity and transition temperatures. In contrast, the organic solvent did influence the film's properties; NMP-containing films had lower glass transition temperatures, adhesion and water resistance than ethanol-based ones. Water-resistance being a desired property, ethanol-based formulations were investigated further for stability, drug release and ungual permeation. The films were stable under accelerated stability testing conditions. Compared to terbinafine, amorolfine was released to a greater extent, had a higher ungual flux, but a lower concentration in the nailplate. However, both drugs were present at considerably high levels in the nail when their MICs are taken into account. We thus conclude that UV-curable gels are promising candidates as topical nail medicines.

Single photon fluorescent microlithography for live-cell imaging.

Using fluorescent dyes to trigger the polymerization of a commercial polyurethane resin allows a rapid fabrication of micrometer and submicrometer sized fluorescent structures by one-photon absorption. Here, we show that standard He-Ne lasers emitting at 632.8 nm can be used to start the photopolymerization and that very low laser power is required. This procedure allows the fabrication of fiduciary fluorescent references on standard glass coverslips, mica sheets, or gold-coated coverslips for laser scanning or standard fluorescent microscopy. The biocompatibility of the polymerized resin with cells in culture was tested by growing Xenopus melanophores and a standard laser scanning microscope was used to demonstrate that it is possible to use equipment readily available in several laboratories. We show that fluorescent structure with less than 10 nm in height may be used as references in fluorescence microscopy allowing a smooth environment for cell growth. Different dyes were tested and the conditions for one-photon polymerization were outlined.

Ultrasound accelerated conversion of Nalpha-urethane protected peptide esters to their thiopeptides using P2S5.

A fast and efficient synthesis of N(alpha)-protected thiopeptide esters from the corresponding peptide esters using P(2)S(5) as thionating agent assisted by ultrasonication has been described. The conversion of peptide bond into thioamide was complete in 20-40 min at rt. The reaction was accomplished without using any base. The products isolated were characterized using (1)H NMR, (13)C NMR and mass spectroscopy.

Study of micro and nano surface structures from UV irradiated urethane/urea elastomers.

In this work we address new results obtained with a thin free standing flexible film (approximately 120 microm) of a urethane/urea copolymer related to the formation of micro and nano size structures [M.H. Godinho, A.C. Trindade, J.L. Figueirinhas, L.V. Melo, P. Brogueira, Synthetic Metals, 147(1-3), 209 (2004); M.H. Godinho, A.C. Trindade, J.L. Figueirinhas, L.V. Melo, P. Brogueira, Molecular Crystals and Liquid Crystals (2005)]. The copolymer was synthesized from a polypropylene oxide-based prepolymer with three isocyanate terminal groups (PU) and polybutadienediol (PBDO) with PBDO content of 40% wt. After casting and curing the film was cut into different samples and each exposed to UV radiation for different periods of time; 23, 25, 26, 31 and 49 h (lambda=254 nm) and later extracted with toluene and dried. The dried films were then studied by polarising optical microscopy (POM), small angle light scattering (SALS) and the surfaces exposed to UV radiation analyzed by means of atomic force microscopy (AFM). Before extraction with toluene a nanometer-flat surface, characterized by a mean roughness value Ra=0.59 nm, was obtained. Depending on exposure time to UV radiation and after extraction with toluene a corrugated surface, with features mum-sized in all axes, resulting in an increase of the overall mean roughness value to Ra=50.7 nm, starts to develop after 25 h of exposure time. This work gives evidence of the non-monotonous time behavior of the wrinkled surface growth that develops under the action of ultraviolet radiation. As the exposure time increases the free-standing films directly exposed surfaces show a decreasing density of the structures observed and an increasing characteristic peak-to-valley height. The peak-to-valley height measured for samples exposed for 23, 25, 26, 31 and 49 h, respectively 193, 383, 381, 1550 and 2039 nm and the corresponding mean roughness values are Ra=50.7 nm, 105.4, 116.8, 438.3 and 515.4 nm, respectively. Between 26 and 31 h exposure time a leap in both values, peak-to-valley and Ra, was observed. The sudden increase in these values is correlated to fabrication of wrinkles by uniaxially stretching PU/PBDO elastomer films.

Chemically nanopatterned surfaces using polyelectrolytes and ultraviolet-cured hard molds.

Polymer transfer printing of poly(acrylic acid) onto a polyelectrolyte multilayer platform resulted in chemically nanopatterned surfaces with well-defined structures and both positive and negative surface functionalities. A commercially available urethane-related photopolymer cured by ultraviolet light was used to make stamps for contact printing with a range of submicrometer down to 80 nm features because of its outstanding mechanical stability and inherent softening transition above 48 degrees C.

The application of magnetic resonance microimaging to the visible light curing of dental resins. 3. Stray-field nuclear magnetic resonance imaging (STRAFI).

OBJECTIVE: To investigate the application of stray-field nuclear magnetic resonance imaging (STRAFI) to the visible light curing of dental restorative materials. STRAFI can overcome peak broadening associated with the conventional magnetic resonance microimaging (MRM) of glassy polymers, and has the potential to image dental restorative resins at both low and high degrees of conversion. METHODS: Cylindrical composite specimens were light-cured from one end to produce some that were fully cured throughout their length and others that were fully cured at one end and uncured at the other. A one-dimensional probe was used to measure the magnetisation in 40 microm thick slices at 100 microm intervals along the length of the specimen. A quadrature pulse sequence was applied and the magnetisation decay recorded in a train of eight echoes. RESULTS: A value for T(2) could be obtained only for the polymer (59+/-16 microms), therefore the echoes were summed to give an approximate indication of the degree of conversion. The echo sum for the monomer was significantly higher than that for the polymer. Differences in composite shade and cure time produced changes in the cure profiles. SIGNIFICANCE: STRAFI produced measurements for both monomer and polymer in all stages of conversion that allowed cure profiles to be produced. Summing the decay echoes produced a qualitative measure of the condition of the material in the selected slice. The same data can be used to calculate T(2), a quantitative parameter. This first investigation has demonstrated that STRAFI is well suited to polymerisation studies.

The relationship between leachability of polymerization initiator and degree of conversion of visible light-cured resin.

Recently, polymerization-initiator-induced radicals have been identified as a biohazard as well as residual monomers. The present investigation was conducted to clarify the leaching behavior of the polymerization initiator and to measure the relationship between the leached amount of polymerization initiator and the degree of conversion of visible light (VL)-cured resin. Moreover, determining a suitable ratio of polymerization initiator to the base monomer according to the above relationship was carried out. The base monomer (UDMA/TEGDMA) was activated with varying concentrations of polymerization initiator (CQ/DMPT, CQ/DMAEMA) from 0.3-0.9 wt%, respectively, which were exposed to light for 40 s. Gas chromatograph mass spectrometry (GCMS) was carried out to evaluate the leached amount of polymerization initiator. The degree of conversion (DC) of the cured sample was estimated using attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy. As the result, it was recognized that the leachability of the polymerization initiator (CQ, DMPT, and DMAEMA) depended on the degree of conversion of the VL-cured resin. Therefore, the optimal concentration of polymerization initiator can be determined from the relation between the degree of conversion and the leached amount of polymerization initiator, which is about 0.6 wt% for CQ/DMPT (1:1 in weight) and 0.5 wt% for CQ/DMAEMA (1:1 in weight) relative to the UDMA/TEGDMA (1:1 in weight) monomer.

Determination of radiation energy emitted by light activation units.

Since the introduction in the 1970s of single paste composite materials, there has been a rapid increase in the range of both materials and activation light units. This investigation is being undertaken as part of a larger study where the characteristics of both composite materials, light activation units and composite material/light activation unit combinations, are being evaluated. This section of the study was undertaken to determine the characteristics of four light activation units. The equipment was developed to measure radiation energy over a wide range of illumination. This range can be from the relatively low intensity of radiation transmitted through restorative materials to the intensities of direct radiation from light activation units. The four light units tested had various radiation outputs between 225,000 lx and 75,000 lx. All the units, apart from one, showed a decrease in light output with successive applications. The units emitted radiation outside the optimum range of 440-500 nm, which may produce damaging radiation and glare. Although the extreme intensities varied threefold the effect on depth of cure of one-material varied by only 16%.