-It is important for toxicological assessment of nanoparticles to determine the penetration of nanoparticle in skin qualitatively and quantitatively. Skin penetration of four different types of rutile titanium dioxide (TiO 2 ) (T-35, 35 nm, non-coating; TC-35, 35 nm, with almina/silica/silicon coating; Tdisp, 10 x 100 nm, mixture of almina coated and silicon coated particles, dispersed in cyclopentasiloxan; T-250, 250 nm, non-coating) was determined with in vitro intact, stripped, and hair-removed skin of Yucatan micropigs to study the effect of dispersion and skin conditions. The TiO 2 was suspended in a volaapplied at a dose 2 μl/cm 2 for 24 hr, followed by cyanoacrylate stripping. The Ti concentration in skin was determined by ICP-MS. T-35 and T-250 easily aggregated in suspension with a mean diameter greater than 1 μm. TC-35 and T-disp showed good dispersion properties with a mean diameter in suspension of approximately 100 nm. No penetration was observed regardless of TiO 2 type in intact and stripped skin.SEM-EDS observation showed that Ti penetrated into vacant hair follicles (greater than 1 mm below the skin surface), however, it did not penetrate into dermis or viable epidermis.

In the present study using a high-intensity X-ray beam from a third-generation synchrotron radiation source, it is demonstrated that a wide-angle X-ray scattering (WAXS) profile from several globular proteins in solution can reflect not only the overall structures (approximately 300 A distance resolution) but also intramolecular structures ranging to secondary structures (approximately 2.5 A distance resolution). The proteins treated in the present experiments are classified as different types of structure categories, namely, as all-alpha, all-beta and alpha + beta proteins. Here the full-range experimental scattering curves are compared with the theoretical curves, suggesting a further availability of the SR-WAXS method for studies of structure hierarchy and the function of proteins in solutions.

The lack of protocols to predict the physical stability has been one of the most important issues in the use of amorphous solid dispersions. In this paper, the crystallization behaviors of pharmaceutical glasses, which have large variations in their crystallization tendencies, have been investigated. Although each compound appears to have a wide variation in their crystallization time, the initiation time for crystallization could be generalized as a function of only Tg/T, where Tg and T are the glass transition temperature and storage temperature, respectively. All compounds in which crystallization was mainly governed by temperature had similar activation energies for crystallization initiation, ca. 210-250 kJ/mol, indicating that physical stability at any temperature is predictable from only Tg. Increased stability is expected for other compounds, where crystallization is inhibited by an large energetic barrier, and stochastic nucleation plays an important role in initiating crystallization. The difference in the dominant factor, either temperature or pressure, appeared to correlate with the nucleation mechanism, and this could be determined by a cool-heat cycle after melting using thermal analysis. This conclusion should make prediction of physical stability of amorphous formulations easier, although the investigation was conducted under ideal conditions, which eliminated surface effects.

Hierarchical features of the thermal unfolding-refolding structural transition of hen egg white lysozyme (HEWL) have been studied in the temperature range from 13 to 84 degrees C by using high-resolution wide-angle X-ray scattering (WAXS) measurements at a third-generation synchrotron source. We have gathered high-statistic WAXS data of the reversible unfolding-refolding process of HEWL in the q range from approximately 0.05 to approximately 3 A(-1) [q = (4pi/lambda) sin(theta/2), where theta is the scattering angle and lambda the wavelength]. This measured q range corresponds to the spatial distance from approximately 2 to approximately 125 A, which covers all hierarchical structures of a small globular protein such as HEWL, namely, tertiary, domain, and secondary structures. Because of this, we have found that the pH dependence of the thermal structural transition of HEWL is well characterized by the various hierarchical levels and the transition concurrence among them. In this report, we present a new hierarchical map depiction of unfolding-refolding transitions. Using scattering with various ranges of q values, we determine the molar ratio of native-like protein structure defined by the data in each range, thus producing a map of the amount of native-like structure as a function of the hierarchical level or resolution. This map can visualize a detailed feature of the unfolding-refolding transition of a protein depending on various structural hierarchical levels; however, the exact meaning of the map will await sharpening by additional works.