Search Results (12)

Background/Objectives: Atractylodes lancea (Thunb.) DC. [Asteraceae] (ALR)-derived exosome-like nanoparticles (ALR-ELNs) exhibit anti-neuroinflammatory effects in microglial cells. However, the associated mechanisms and pathways are unknown. We aimed to characterize the effects of ALR-ELNs on inflammatory responses of BV-2 microglial cells to lipopolysaccharide (LPS) using RNA sequencing. Methods: ALR-ELNs were fractionated from ALR. BV-2 microglial murine cells were stimulated with LPS after treatment with ALR-ELNs. RNA sequencing was performed to analyze variations in mRNA levels. Ingenuity pathway analysis (IPA) was performed to investigate the mechanism of action of ALR-ELNs. mRNA expression was assessed using real-time quantitative polymerase chain reaction (qPCR). Results: The expression of 651 genes was downregulated, whereas that of 1204 genes was upregulated in LPS-stimulated BV2 cells pretreated with ALR-ELNs. The IPA showed that the effects of ALR-ELNs on inflammation took place through pathogen-influenced signaling. Network analysis via IPA showed that the Toll-like receptor (TLR) is involved in the suppression of inflammation by ALR-ELNs. The qPCR analysis showed that pretreatment with ALR-ELNs significantly reduced TLR4 mRNA expression. Conclusions: ALR-ELNs suppress the release of inflammatory mediators by downregulating TLR4 expression, which is a novel mechanism by which ALR-ELNs act on microglia. Identifying active ingredients in ALR-ELNs that downregulate TLR4 expression can advance the development of therapeutic drugs for neuroinflammatory diseases. Full article

The study aims to assess the usefulness of human T-cell leukemia virus type 1 (HTLV-1)-infected cell analysis using flow cytometry (HAS-Flow) as a monitoring method for adult T-cell leukemia (ATL) development in HTLV-1-positive patients with rheumatoid arthritis (RA) under treatment with antirheumatic therapies. A total of 13 HTLV-1-negative and 57 HTLV-1-positive RA patients participated in this study, which was used to collect clinical and laboratory data, including HAS-Flow and HTLV-1 proviral load (PVL), which were then compared between the two groups. CADM1 expression on CD4+ cells in peripheral blood (PB) was used to identify HTLV-1-infected cells. The population of CADM1+ CD4+ cells was significantly higher in HTLV-1-positive RA patients compared to HTLV-1-negative RA patients. The population of CADM1+ CD4+ cells was correlated with HTLV-1 PVL values. There were no antirheumatic therapies affecting both the expression of CADM1 on CD4+ cells and PVLs. Six HTLV-1-positive RA patients who indicated both high HTLV-1 PVL and a predominant pattern of CADM1+ CD7neg CD4+ cells in HAS-Flow can be classified as high-risk for ATL progression. HAS-Flow could be a useful method for monitoring high-risk HTLV-1-positive RA patients who are at risk of developing ATL during antirheumatic therapies. Full article

Mefenamic acid (MFA), a water-insoluble drug, is used as a suspension in the medical field, but it requires shaking before using to disperse MFA content in the suspension. In previous studies, trials to prepare MFA suspension with high dispersion stability by atomizing MFA by the wet-milling method. However, HPC is used for atomizing MFA. Therefore, the optimum concentration and molecular weight for atomizing MFA have not been investigated. In this study, we investigated the optimum molecular weight and concentration of HPC for the micronization of MFA. As a result, MFA particles became fine particles by adding SDS, and the particle size was also smaller than that of HPC alone. In addition, the suspension with the highest dispersion stability can be obtained when a mixed solution of 1.0% HPC-SL and 0.12% SDS aqueous solution is used. Therefore, this study considers that the addition of SDS and 1.0% HPC-SL aqueous solution are optimal for improving the dispersion stability of the MFA suspension. Full article

In Japan, rebamipide (RB) mouthwash (RB-MW) for oral mucositis induced by cancer chemotherapy has been prepared using in-hospital formulation. Usually, RB-MW is prepared by dispersing crushed commercial RB tablets in the dispersion medium; however, uniformity is difficult to obtain due to low solubility. The current study aims is to prepare homogenously dispersed formulations using the fine particles of crushed tablets by a method that is convenient for hospital use. Commercial RB tablets were pre-milled at different milling times as “RB-Ts”. A ground mixture was then prepared by co-grinding the RB-Ts with HPC-L or PVP K30 via a benchtop ball milling machine (MM400). The physicochemical properties of samples were evaluated for PXRD, FTIR, turbidity, particle size, and solubility. Although the milling of RB tablets decreased the crystallinity, the length of milling time did not affect them. In contrast, grinding using MM400 significantly decreased RB crystallinity; their PXRD patterns showed a halo, suggesting the amorphization of RB crystals by grinding. Although solubility and turbidity seemed to be affected by the type of polymer rather than the particle size, every ground mixture showed high dispersibility. Thus, grinding the RB-Ts with polymers appeared to be the most promising way to obtain stable dispersion as an in-hospital formulation. Full article

The solubility of a drug is higher when it is in an amorphous form than when it is in a crystalline form. To enhance the solubility of ibuprofen (IBU), a poorly water-soluble drug, we attempted to adsorb IBU onto spherical porous calcium silicate (Florite^® PS300, PS300) in two ways: the evaporation (EV) and sealed heating (SH) methods. The crystallinity of the samples was evaluated using powder X-ray diffraction analysis (PXRD) and differential scanning calorimetry (DSC). The molecular interaction between IBU and PS300 was evaluated with FTIR. In addition, the dissolution behavior of IBU in the samples was assessed by the dissolution test. Based on the results of the PXRD and DSC measurements, both methods allowed adsorption of IBU onto PS300, and IBU was amorphized. Based on the FTIR observations, in the SH or EV mixtures containing 10% and 30% IBU, respectively, it seemed that the IBU molecules intermolecularly interacted with calcium molecules as the main component of PS300. Improvement in the solubility of IBU was observed with both methods; however, the dissolution rate of IBU from samples prepared via SH was higher than that from EV, or of IBU crystals. Collectively, our findings indicate that the petal-like structure of PS300, which has a spherical shape and good flowability, is an effective tool for adsorbing IBU onto PS300 via SH. Full article

In clinical practice, for elderly or pediatric patients who have difficulty swallowing, solid dosage forms such as tablets or capsules are crushed or unsealed, prepared as powder forms, and often administered as suspensions. However, because their dispersibility is poor, aggregation or precipitation occurs readily. Once precipitation and deposition happen, redispersion is difficult, which can limit patient and caretaker drug adherence. In this study, we attempted to prepare nanoparticles as a hospital formulation by a benchtop wet-milling method to obtain a suspension with high dispersibility. This is the first study to apply the wet-milling method to prepare the hospital formulation. We chose cefditoren pivoxil (CDTR-PI) as an experimental active pharmaceutical ingredient. CDTR-PI crystals were physically mixed with various water-soluble polymers such as polyvinylpyrrolidone, polyethylene oxide, hydroxypropyl cellulose, or hypromellose and wet-milled with a surface-active agent (sodium lauryl sulfate) under different conditions. The mean particle diameter of most of the samples was less than 200 nm. In FTIR spectra of ground samples, peak shifts suggesting inter- or intramolecular interactions between CDTR-PI and the other additive agents were not observed. Besides, the nanoparticle suspension had favorable dispersibility, as determined using a dispersion stability analyzer. Providing a suspension with high dispersibility makes dispense with the resuspension, the patient’s medication adherence would improve. These results show that suspended liquid formulations of active pharmaceutical ingredients could be obtained by the simple wet-milling method as hospital formulations. Full article

Hyaluronic acid (HA) has been known to play an important role in wound healing process. However, the effect of molecular weight (MW) of exogenously administered HA on the wound healing process has not been fully understood. In this study, we investigated HA with different MWs on wound healing process using human epidermal keratinocytes and dermal fibroblasts. Cell proliferation and migration ability were assessed by water soluble tetrazolium (WST) assay and wound scratch assay. We examined the effect of HA addition in a full-thickness wound model in mice and the gene expression related to wound healing. Proliferation and migration of HaCaT cells increased with the increase of MW and concentration of HA. Interleukin (IL-1β), IL-8 and vascular endothelial growth factor (VEGF) as well as matrix metalloproteinase (MMP)-9 and MMP-13 were significantly upregulated by high molecular weight (HMW) HA in keratinocytes. Together with VEGF upregulation and the observed promotion of HaCaT migration, HA with the MW of 2290 kDa may hold potential to improve re-epithelialization, a critical obstacle to heal chronic wounds. Full article

Solubility is an important physicochemical property affecting drug bioavailability. One approach to improve drug solubility is using amorphous formulations, which can improve solubility by up to a 1000-fold. Herein, amorphous curcumin (CUR) and amorphous solid dispersions (SDs) consisting of CUR, hydroxypropyl cellulose (HPC) and/or sodium dodecyl sulfate (SDS) were developed using vibrational ball milling. The resulting ground mixtures (GMs) were characterized using powder X-ray diffractometry, Fourier transform infrared spectroscopy, differential scanning calorimetry and a dissolution test. The 60-min GM containing 90% HPC significantly increased the drug solubility. Presence of SDS in the GMs containing 90% HPC reduced the grinding duration from 60 min to 30 min in forming a ground SD that significantly increased the CUR dissolution rate. This amorphous state was stable for 30 days when stored at 40 °C/RH 75%. Full article

Cyclodextrins (CDs) and their derivatives significantly increase drug solubility by forming drug/CD complexes known as solid dispersions (SDs), which consist of an inclusion complex (IC), where the drug is entrapped within the CD cavity, and a non-IC. Here, the SDs of curcumin (CUR) and hydroxypropyl-β-cyclodextrin (HPβCD) were prepared using the grinding, freeze-drying (FD), and common solvent evaporation (CSE) methods and were physicochemically characterized using solubility, powder X-ray diffraction, Fourier transform infrared, differential scanning calorimetry, and dissolution studies. The second or higher order complex of CUR-HPβCD indicated the co-existence of ICs and non-ICs known as the SD system. When comparing the soluble drug amount with CUR crystals, the solubility of SDs was enhanced by up to 299-, 180-, and 489-fold, corresponding to the ground mixtures (GMs), freeze-drying mixtures (FDs), and common solvent evaporation mixtures (CSEs), respectively. The total transformation into the amorphous phase of CUR was observed in GMs and in CSE12, CSE14, and CSE18. The drug was well dispersed within HPβCD in GMs and CSEs, suggesting the formation of hydrogen bonds between CUR and HPβCD, whereas the dispersed behavior of FDs was similar to that of physical mixtures. In SDs, the melting temperature of CUR was in an increased order of CUR in 1:2 ICs, CUR in 1:1 ICs, and CUR crystals. The dissolution rate of CUR was positively improved as the amount of HPβCD in SDs increased. The SD system consisting of CUR and HPβCD significantly increased the drug solubility compared to ICs. Full article

Aphthous stomatitis is one of the side effects of chemotherapy and radiotherapy in cancer treatment. Rebamipide (RB) mouthwash for stomatitis acts as a radical scavenger. However, RB is poorly soluble in water, which leads to aggregation and precipitation of the dispersoid. The particle size of the drug needs to be less than 100 nm for the particles to reach the mucus layer in the oral cavity. In this study, we attempted to prepare nanoparticles of RB by cogrinding with polyvinylpyrrolidone (PVP) or hydroxypropyl cellulose (HPC) and sodium dodecyl sulfate (SDS) using a mixer ball mill, and evaluated the physicochemical properties of RB nanoparticles, the stability of dispersion in water, and permeation of the mucus layer in vitro. By cogrinding, the particle size decreased to around 110 nm, and powder X-ray diffraction (PXRD) of the particles showed totally broad halo patterns, which suggested a decreased crystalline region. Furthermore, the solubility of RB nanoparticles increased by approximately fourfold compared with RB crystals, and the water dispersibility and permeation of the mucus layer were improved. The results suggest that in a ternary ground mixture of RB, PVP or HPC, and SDS, the RB nanoparticles obtained can be applied as a formulation for stomatitis. Full article

Consideration of drug usability characteristics is important during the design process. Although many wound management products have been developed in recent years, there are few studies on their usability. We investigated the needs and characteristics of wound management products required by medical professionals, so as to consider these in future development projects. Semi-structured interviews were conducted in a group of healthcare professionals. Interview responses were analyzed based on thematic analysis. Four themes common to all facilities were secondary wounds, adaptability of materials, convenience, and physicochemical properties. Economic efficiency of medical care was found to be considered only at the hospital, and quality of life of patients was found to be considered only at the home palliative care clinic. Requirements for wound management products can be affected by participants’ roles and their facility settings. However, there were needs common to all fields that all wound management products should aim to incorporate. Full article

This study aimed to investigate the effect of polymers and storage relative humidity on amorphous rebamipide (RB) and its solid dispersion phase transformation using chemometrics based on multiple datasets. The amorphous RB was prepared using particle mixture and grinding methods with hydroxypropyl cellulose, polyvinylpyrrolidone, and sodium dodecyl sulfate. Prepared amorphous RB and solid dispersion samples were stored under a relative humidity of 30% and 75% for four weeks. Infrared spectra of the dispersion samples suggested that the hydrogen bond network was constructed among quinolinone, carbonyl acid, and amide of RB and other polymers. The dataset combining near-infrared (NIR) spectra and powder X-ray diffractograms were applied to principal component analysis (PCA). The relationship between diffractograms and NIR spectra was evaluated using loadings and the PCA score. The multiple spectra analysis is useful for evaluating model amorphous active pharmaceutical ingredients without a standard sample. Full article