Shoichi Shirotake

Effect of anionic and cationic n-butylcyanoacrylate nanoparticles on NO and cytokine production in Raw264.7 cells.

Context: Research on drug delivery carriers that use nanoparticles is currently attracting a great deal of attention. In order to evaluate the safety of these drug carriers for clinical applications, a full assessment of their toxicity and bioactivity is required. Although it is well-known that the surface charge of nanoparticles influences their bioactivity, most of the published studies on n-butylcyanoacrylate (NBCA) nanoparticles as a potential drug delivery carrier are restricted to analyzing the anionic form. Objective: We compared biological responses of cyanoacrylate anionic nanoparticles with cationic nanoparticles in cultured murine macrophages for assessing cytotoxicity and inflammatory responses. Materials and methods: The cytotoxicity was evaluated with the MTS and LDH leakage assays. Inflammatory responses were evaluated by measurement of nitric oxide (NO), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α). The interaction of the nanoparticle and the macrophage was assessed by fluorescence microscopy. Result: Anionic and cationic NP showed no detectable cytotoxicity at a concentration of 10 µg/mL or less. At concentrations greater than 10 µg/mL, cationic NP displayed lower cytotoxicity by comparison with anionic NP. NO, IL-6, and TNF-α production were not induced by anionic or cationic nanoparticles alone. In contrast, both types of nanoparticles decreased NO, IL-6, and TNF-α productions induced by LPS. However, the anti-inflammatory effect of anionic nanoparticles was significantly greater than that of cationic nanoparticles. Nanoparticles were presumed to be either internalized or attached to the cell membranes. Discussion and conclusion: NBCA nanoparticles are not only important as potential drug carriers but also as promising anti-inflammatory agents that may have therapeutic properties.

Bacteriolysis by vancomycin-conjugated acryl nanoparticles and morphological component analysis

Abstract Nanoparticles are currently attracting considerable attention because of their ability to conjugate to various substances. As such, these nanoparticles can assist the transfer of the conjugated substance to target tissues where they are gradually released. In this study, vancomycin-conjugated nanoparticles (VCM NPs) were prepared. The antibacterial activity of VCM NPs was compared with that of VCM alone by exposure to vancomycin-resistant enterococci (VRE). The morphology of the cells was then analyzed by electron microscopy. VCM NPs were found to have more potent antibacterial activity against VRE compared to VCM alone, but the activity against vancomycin-sensitive enterococci (VSE) remained the same. The antibacterial activity of nanoparticles alone was the same against VSE and VRE. The nanoparticles were found to induce characteristic morphological changes in the bacteria based on scanning and transmission electron microscopy. The results suggest that the strong antibacterial activity of VCM NPs against VRE may be attributable not only to the well-known control release carrier property of the nanoparticles but to an additional mechanism that involves VCM NPs avoiding the drug resistant mechanism of VRE.

Effect of Sodium Caprate on the Absorption of Progesterone from Mixed Suppositories Administered to the Vagina of Rabbits

The promoting effect of sodium caprate (CAP) added to a progesterone mixed suppository was investigated in vitro and in vivo. The mixed suppository (S50), consisting of Witepsol W35 and ethylene-vinyl acetate copolymers (EVA40Y and EVA250); and a control suppository of Witepsol W35 (C50) were prepared by the fusion method. One or five percent of CAP was added to S50 and C50 containing 50 mg of progesterone. The release of progesterone from C50 was not influenced by the addition of CAP and there was no change in plasma level profile of progesterone after administration to the vagina of rabbits. On the other hand, S50 added with CAP showed rapid elevation of the plasma level of progesterone without any change in the sustained-release characteristics.

Dissolution Profiles of Glibenclamide Tablet Using Flow-Through-Cell Method

Operating conditions affecting the dissolution characteristics of glibenclamide were investigated with the flow-through-cell method (the third method of dissolution test in JP XIII). The partition coefficient of glibenclamide between octanol and phosphate buffer (pH 7.4) was observed to be 24.2, thus suggesting the lipophilic nature of glibenclamide. The flow indicator on the apparatus in the flow-through-cell method did not reflect the real flow rate of the dissolution media.The dissolution-time curve (ADT) value increased in line with the decrease in the beads diameter when the flow rate of the indicator was slow (8 ml/min). On the other hand, the ADT value was hardly affected by the beads diameter when the flow rate was fast (24 ml/min), however, a wide deviation in the ADT values was seen during such conditions. The operating condition of flow rate and beads diameter was optimized based on the response surface method. As a result, a flow rate of 14 ml/min and a bead diameter of 0.5 mm were estimated as the optimal conditions to obtain the largest ADT and the smallest deviation in the ADT. When using the fl ow-through-cell method, the operating condition should be optimized based on the nature of pharmaceuticals under test.

Preparation of Zinc Pyrithion Lotion as a Hospital Preparation and Evaluation of its Physical Characteristics.

In order to treat psoriasis, many kinds of drugs are administered systemically and topically. However, the topical admimistration of drugs is preferred to the systemic administration because the former can occasionally cause serious side effects. Zinc Pyrithione (ZPT), which is recognized as an active ingredient in a major anti-dandruff shampoo, was introduced as a new antipsoriatic agent. In this study, ZPT lotions as a hospital preparation were prepared for topical administration.Hydroxypropylcellulose-H (HPC), sodium-polyacrylate (PANA) and carmellose sodium (CMC) were used as a suspending agent of 0.5% ZPT lotion. The following physical characteristics, the viscosity, the osmotic pressure, the sedimentation, the microscopic view and the dispersion were investigated in each ZPT lotion containing different suspended agents.The viscosity of the ZPT lotion with HPC and CMC increased with the additive ratio of these suspended agents. On the other hand, the viscosity of the ZPT lotion with PANA increased logarithmically with its additive ratio. The low osmotic pressure of each lotion was expected to be less irritable in clinical application. When ZPT lotions were stored at room temperature for 14 days, the lotion with HPC or CMC showed free sedimentation and caking of the particles. In contrast, the lotion with PANA showed a growth of particles by a microscopic analysis and coagulated sedimentation by macroscopy. These phenomena may be due to the ionic intensity of the solution and the interaction between ZPT particles. The dispersion time of ZPT lotions with PANA was shorter than those with HPC or CMC.Based on our findings, 0.2% PANA was found to be preferable to HPC and CMC as the suspended agent in ZPT lotion.