Comparative pharmacokinetics of maxacalcitol in healthy Taiwanese and Japanese subjects.

Pharmacokinetic studies of maxacalcitol in healthy Taiwanese subjects have been conducted. This study to compare the pharmacokinetic properties of maxacalcitol in healthy Taiwanese and Japanese subjects. Healthy male Taiwanese subjects (n = 24) and healthy male Japanese subjects (n = 24) were enrolled in separate single-center and received a single intravenous dose of 1.25, 2.5 and 5 µg maxacalcitol. Male subjects were exclusively employed in the study due to the first administration of maxacalcitol to Taiwanese. Serum samples were collected for up to 72 h for pharmacokinetic analysis, and safety was assessed. Exposures to maxacalcitol as mean C5 and AUCinf appeared to increase with increase of doses in Taiwanese subjects (C5: 74.0, 159, and 321 pg/mL; AUCinf: 473, 763, and 1460 hï½¥pg/mL) and Japanese subjects (C5: 92.9, 174, and 346 pg/mL; AUCinf: 312, 588, and 1040 hï½¥pg/mL). After single bolus IV administration, linearity in maxacalcitol exposure was shown over the dose range of 1.25-5 µg in both Taiwanese and Japanese male healthy subjects. C5 of maxacalcitol was slightly lower (85%) in Taiwanese compared with that in Japanese and AUCinf of maxacalcitol in Taiwanese subjects was contrarily 15.0 (41.6%) higher than that in Japanese subjects, resulted in not much difference in pharmacokinetics of maxacalcitol between Taiwanese and Japanese. Moreover, maxacalcitol was well tolerated in both healthy Taiwanese and Japanese subjects.

Micron- and nano-sized poly(N-isopropylacrylamide-co-acrylic acid) latex syntheses and their applications for controlled drug release.

Thermo-sensitive poly(N-isopropylacrylamide-co-acrylic acid) (P(NIPAAm-co-AAc)) latex particles were prepared with and without sodium dodecyl sulfate (SDS) surfactant via an emulsion polymerization method. The P(NIPAAm-co-AAc) latex particle sizes were approximately 1.1 microm without SDS addition and the particle sizes were in the nanometer range (59 nm) with SDS at its critical micelle concentration (CMC) of 8 mM. We propose a scheme to demonstrate how the SDS concentration affects the synthesized latex particle size. The lower critical solution temperature (LCST) was hardly influenced by the SDS level but increased with the AAc concentration. The PNIPAAm-co-AAc latex particles were employed as thermo-sensitive drug carriers and 4-acetamidophenol was loaded to study the drug release rates from the nano-gels. The effective drug diffusion coefficients within the nano-gels varied as a function of particle size, AAc content, and temperature. The smaller or AAc-rich hydrogel particles provided sustainable drug release property and have potential use in biomedical applications.

Time-resolved polymer propagation for acrylic acid-mediated nanolatexes containing magnetic Fe3O4 cores.

This study reports on the time-resolved polymer propagation of thermal-sensitive latex nanoparticles containing Fe3O4 cores. The latex shells are made with poly(N-isopropylacrylamide-co-acrylic acid) (Fe3O4/P(NIPAAm-co-AAc)) at different reaction times. The Fe3O4 particles are first modified using AAc monomers. The AAc-modified Fe3O4 cores are then copolymerized with NIPAAm to form the latex shell. The Fe3O4 cores in the latex nanoparticles are confirmed using X-ray photoelectron spectroscopy (XPS), X-ray diffraction spectroscopy (XRD), and thermo gravimetric analyzer (TGA). As the reaction time is increased from 0.5 h to 2 h, the particle size enlarges from 100 to 250 nm and the Fe3O4 content decreases from 46.4% to 2.6%. The thermal responses are more pronounced in the 2 h sample with the phase transition temperature (lower critical solution temperature, LCST) about 35 degrees C. The nanoparticles show a gradient concentration distribution of AAc as the particles propagate. A higher AAc concentration is observed near'the Fe3O4 core and the AAc content deceases as the degree of polymerization increases in the latex particles. This declining AAc concentration is beneficial for profound thermal responses in the synthesized nanoparticle.

In vitro biocompatibility of magnetic thermo-responsive nanohydrogel particles of poly(N-isopropylacrylamide-co-acrylic acid) with Fe3O4 cores: effect of particle size and chemical composition.

Biocompatibility is a critical factor in the design and development of candidate materials for biomedical use. This paper reports on the in vitro biocompatibility of magnetic stimuli-sensitive nanohydrogel particles composed of magnetite cores in poly(N-isopropylacrylamide-co-acrylic acid) shells referred to Fe(3)O(4)/P(NIPAAm-co-AAc). The AAc concentration and polymerization time were varied to fabricate magnetic nanoparticles with various AAc levels (1.80-2.37%) and particle sizes (74-213 nm). The P(NIPAAm-co-AAc) shell exhibited thermo-sensitive properties and the Fe(3)O(4) core constituted 2.25-4.10% of the particles by weight. After a 2-day incubation of L929 cells with extract media that had been conditioned with various test samples, the cellular responses were monitored in terms of cell viability and growth. The Live/Dead assays showed that high levels of cellular viability (97.3-98.1%) were observed in all groups, indicating that none of the nanoparticles were cytotoxic. However, the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymetho-xyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assays demonstrated that the activity of mitochondrial dehydrogenase varied significantly in cultures exposed to different magnetic nanohydrogel particles. The murine fibroblasts exposed to the NIP-(AAc5.1-Fe)-2 sample, which contained the highest AAc content and largest particle sizes, were the least metabolically active. In contrast, the activity levels in the cultures treated with the low AAc content and small size particles (NIP-(AAc2.6-Fe)-1) were not significantly different from those in the control group. Our findings suggest that smaller magnetic stimuli-sensitive nanohydrogel particles with a lower AAc content may have little inhibitory impact on cell proliferation. Overall, the in vitro biocompatibilities of the nanoparticles depend on the chemical composition and size of the Fe(3)O(4)/P(NIPAAm-co-AAc) particles.