Robust Nanoparticle Morphology and Size Analysis by Atomic Force Microscopy for Standardization.

Because of the complexity of nanomedicines, analysis of their morphology and size has attracted considerable attention both from researchers and regulatory agencies. The atomic force microscope (AFM) has emerged as a powerful tool because it can provide detailed morphological characteristics of nanoparticles both in the air and in aqueous medium. However, to our knowledge, AFM methods for nanomedicines have yet to be standardized or be listed in any pharmacopeias. To assess the applicability of standardization of AFM, in this study, we aimed to identify robust conditions for assessing the morphology and size of nanoparticles based on a polystyrene nanoparticle certified reference material standard. The spring constant of the cantilever did not affect the size of the nanoparticles but needed to be optimized depending on the measurement conditions. The size analysis method of the obtained images affected the results of the analyzed size values. The results analyzed by cross-sectional line profiling were independent of the measurement conditions and gave similar results to those from dynamic light scattering. It was indicated that approximately 100 particles are required for a representative measurement. Under the optimized conditions, there were no significant inter-instrument differences in the analyzed size values of polystyrene nanoparticles both in air and under aqueous conditions.

Binding affinities of paclitaxel and docetaxel for generic and nanoparticle albumin-bound paclitaxel-derived albumin from human serum.

Nanoparticle albumin-bound (nab)-paclitaxel is a 130-nm formulation containing human serum albumin (HSA). The clinical efficacy of this formulation is considered to depend on its affinity for HSA. The high pressure employed during the manufacture of nab-paclitaxel HSA (nab HSA) may influence its conformation and/or oligomerization, and ultimately its affinity for HSA. Therefore, studies are required to evaluate whether the affinity of paclitaxel for nab HSA is similar to that of generic HSA (control HSA). In the present study, nab HSA was isolated from nab-paclitaxel by gel filtration, and the binding affinities (KDs) were determined by surface plasmon resonance. Furthermore, the affinity of docetaxel for nab HSA and control HSA was measured, as their binding sites are similar. Paclitaxel showed KDs of 8.93±8.60 and 7.39±5.81 µM for nab HSA and control HSA, respectively, whereas the corresponding KDs for docetaxel were 44.3±9.50 and 55.9±2.28 µM, respectively. This suggests that the paclitaxel binding site was not modified during the nab-paclitaxel manufacturing process. Additionally, nab HSA likely does not affect paclitaxel and blood HSA binding, as evidenced by the similar affinities of paclitaxel and docetaxel for nab HSA and control HSA. In conclusion, the binding affinities of paclitaxel and docetaxel for nab HSA and control HSA were found to be comparable. Additionally, the manufacturing process did not influence the paclitaxel binding affinity for nab HSA. These results also suggest that nab HSA may not affect the clinical effectiveness of nab-paclitaxel.

Water-proton relaxivities of DNA oligomers carrying TEMPO radicals.

5-Uridine derivative carrying a TEMPO radical (UST) was prepared and its single strand (ssUST) and a double strand (dsUST) with its complementary strand were obtained. Similarly, single strands carrying two and five radicals (ssUST2 and ssUST5, respectively) and the corresponding double strands (dsUST2 and dsUST5) were prepared. Their electron paramagnetic resonance (EPR) spectra showed typical anisotropic broadening in the high field line. The rotational correlation times, tau(R), estimated by analyzing the EPR spectra are 1.1 x 10(-10), 5.9 x 10(-10), and 14 x 10(-10) s for UST, ssUSTm, and dsUSTm, respectively. The water-proton relaxivities, r(1) and r(2), at 25 MHz, 0.59 T, and 25 degrees C, also increased in the same order and the r(1) values were 0.26, 0.41, and 0.56 mM(-1) s(-1) for UST, ssUSTm, and dsUSTm, respectively. The r(1) values of 1.00 and 2.06 mM(-1) s(-1) for dsUST2 and dsUST5, respectively, were obtained.

Effects of Contact Angle and Flocculation of Particles of Oligomer of Tetrafluoroethylene on Oil Foaming.

Oil foams have been stabilized by using particles of oligomer of tetrafluoroethylene (OTFE). OTFE particles were dispersed in oil mixtures prior to aeration, to exclude the oil-repellency nature of the particles due to the formation of the metastable Cassie-Baxter state and properly evaluate the effects of contact angle on the foaming behavior. The particle contact angle (θY) against air/oil surfaces were controlled by changing a composition of two oils with different surface tension (n-heptane and methyl salicylate). The θY value increases with increasing a mole fraction of methyl salicylate, from 42° (for pure n-heptane) to 89° (for pure methyl salicylate). The air volume incorporated in the oils after aerating OTFE dispersions in the oil mixtures shows a maximum when θY = 55°. The flocculation of OTFE particles in bulk oils is responsible for the unexpected behavior of foaming observed when θY is relatively high. The increase in the degree of the flocculation reduces the effective concentration of OTFE particles in bulk oil, leading to the inefficient bubble stabilization. These findings suggest the efficient oil foaming using particles as a stabilizer is achieved by optimizing both the particle contact angle and the degree of flocculation in oils.

Synthesis and relaxivities of oligonucleotides with TEMPO-labeled sugar moiety.

5-Uridin derivative, UUT, having TEMPO radical at the 2'-position of sugar moiety, was prepared and characterized by X-ray crystallography. The single strands, ssUUT, incorporating UUT and the double strands, dsUUT, with complimentary strand were also obtained. Their EPR spectra and relaxivities (25 MHz and 0.59 T) in water were measured. The values of tau R obtained from the simulation of EPR spectra and the water-proton relaxivities, r1 and r2, increased in order of UUT, ssUUT, and dsUUT.