PurposeWe designed formulations based on minoxidil (MXD) nanoparticles (N-MXD) and examined whether N-MXD can increase drug delivery into the follicles. In addition, we investigated the effect of N-MXD on hair growth in C57BL/6 mice.MethodsN-MXD (1%) was prepared as follows: methylcellulose, p-hydroxyalkylbenzoates, mannitol, and MXD were dispersed in purified water and milled using zirconia beads under refrigeration (5500 rpm, 30 s×15 times, intermittent milling). C57BL/6 mice were used to evaluate hair-growth effects. The expression levels of mRNA and protein for vascular endothelial growth factor (VEGF) and insulin-like growth factor-1 (IGF-1) were determined by real-time PCR and ELISA methods, respectively.ResultsThe ratio of solid-MXD was approximately 60% in N-MXD, and the MXD nanoparticles (90–300 nm) were oblong in shape. For the design of nanomedicines, usability is important. Therefore, we measured the stability and toxicity after N-MXD treatment. No agglutination of MXD nanoparticles was detected for 2 weeks, and no redness or MXD powder residue was observed in the skin after repetitive applications of N-MXD. Next, we evaluated hair-growth effects by N-MXD treatment. MXD contents in the skin tissue from N-MXD were lower than for commercially available MXD formulations (CA-MXD). Conversely, MXD contents in the hair bulbs were higher for N-MXD than for CA-MXD, and the drug efficacy of N-MXD was also higher than that of CA-MXD. In addition, the mRNA and protein levels of IGF-1 and VEGF were enhanced by the repetitive application of N-MXD and CA-MXD, and the enhanced IGF-1 and VEGF levels were significantly higher for N-MXD than for CA-MXD.ConclusionWe designed a novel nanomedicine based on MXD nanoparticles and showed that N-MXD can deliver MXD into hair bulbs via hair follicles and that the therapeutic efficiency for hair growth is higher than for CA-MXD (solution type).
We previously found the instillation of sericin to be useful as therapy for keratopathy with or without diabetes mellitus. In this study, we investigated whether a combination of solid magnesium hydroxide nanoparticles (MHN) enhances epithelial corneal wound healing by sericin using rabbits, normal rats and type 2 diabetes mellitus rats with debrided corneal epithelium (ex vivo and in vivo studies). Ophthalmic formulations containing sericin and MHN (N-Ser) were prepared using a bead mill method. The mean particle size of the N-Ser was 110.3 nm at the time of preparation, and 148.1 nm one month later. The instillation of N-Ser had no effect on the amount of lacrimal fluid in normal rabbits (in vivo), but the MHN in N-Ser was found to expand the intercellular space in ex vivo rat corneas. In addition, the instillation of N-Ser increased the phosphorylation of Extracellular Signal-regulated Kinase (ERK)1/2, a factor involved in cell adhesion and cell proliferation in the corneal epithelium, in comparison with the instillation of sericin alone. The combination with MHN enhanced epithelial corneal wound healing by sericin in rat debrided corneal epithelium (in vivo). This study provides significant information to prepare potent drugs to cure severe keratopathy, such as diabetic keratopathy.
Synopsis:Rate of melting of partly reduced iron pellets into iron melt was obtained by measuring CO gas evolved. The effects of composition of pellets as well as temperature and carbon content of iron melt on their melting rate into the melt have been investigated. The following results are obtained:(1) Apparent activation energy of melting of reduced iron pellets containing 0,10,20 and 40% Fe2O3 was 33 kcal/mol.(2) Without slag melt on the iron melt, the maximum melting rate of pellets containing 10,20 and 40% Fe2O3 was obtained at about 3.3, 3.0 and 2.5% carbon contents respectively.(3) Melting rate was proportional to -0.5 power of Fe2O3 content at the range of 15-60%Fe2O3, increased at 2-10% Fe2O3 and decreased above 70% Fe2O3.(4) CaO, CaCO3 or C of 2-5% as addititive increased the melting rate of pellets, but addition of Al2O3 or SiO2 decreased it extremely. Simultaneous addition of CaO and SiO2 (CaO/SiO2=1) and addition of pre-fused slag whose melting point was low decreased the melting rate slightly up to 5%, and their content in pellets should be limited within 15%.
SynopsisFor the purpose of the process control in continuous steelmaking, a new method of G. P. (Giant Pulse) laser direct spectrochemical analysis of C, Si, and Mn in liquid iron has been developed. This method is characterized by coincidence of optical axes of laser and spectrometer. In this study, fundamental conditions for the analysis of C, Si, and Mn, especially taking a serious view of C, have been studied. The following results have been obtained:(1) Influence of variations in the level of liquid iron surface on spectral intensities and intensity ratios has been evaluated. It has been shown that, for the purpose of minimization of these influences, intensity ratio should be used.(2) Si and Mn analyses are possible with the use of cylinder type and cone type atmosphere controlling apparatus.(3) In C analysis, it has been shown that CO gas generated in the surface of liquid iron has effects upon spectral intensity of CI 193.1 nm, and these effects can be eliminated by using cone type atmosphere controlling apparatus. C analysis is possible with the use of this apparatus.
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