Targeting miR-223 in neutrophils enhances the clearance of Staphylococcus aureus in infected wounds

Abstract Argonaute 2 bound mature microRNA (Ago2‐miRNA) complexes are key regulators of the wound inflammatory response and function in the translational processing of target mRNAs. In this study, we identified four wound inflammation‐related Ago2‐miRNAs (miR‐139‐5p, miR‐142‐3p, miR‐142‐5p, and miR‐223) and show that miR‐223 is critical for infection control. miR‐223Y/− mice exhibited delayed sterile healing with prolonged neutrophil activation and interleukin‐6 expression, and markedly improved repair of Staphylococcus aureus‐infected wounds. We also showed that the expression of miR‐223 was regulated by CCAAT/enhancer binding protein alpha in human neutrophils after exposure to S. aureus peptides. Treatment with miR‐223Y/−‐derived neutrophils, or miR‐223 antisense oligodeoxynucleotides in S. aureus‐infected wild‐type wounds markedly improved the healing of these otherwise chronic, slow healing wounds. This study reveals how miR‐223 regulates the bactericidal capacity of neutrophils at wound sites and indicates that targeting miR‐223 might be of therapeutic benefit for infected wounds in the clinic

Microparticulated Mefenamic Acid with High Dispersion Stability for Pediatric Dosage Form

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

Preparation and Evaluation of a Powdered Rebamipide Mouthwash as In-Hospital Formulation: Considering Dispersion before Use in Patients

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

Preparation and Characterization of Solid Dispersions Composed of Curcumin, Hydroxypropyl Cellulose and/or Sodium Dodecyl Sulfate by Grinding with Vibrational Ball Milling

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%