Journal: Cells

Article Title: In Situ Gel Incorporating Disulfiram Nanoparticles Rescues the Retinal Dysfunction via ATP Collapse in Otsuka Long–Evans Tokushima Fatty Rats

doi: 10.3390/cells9102171

Figure Lengend Snippet: Composition of ophthalmic disulfiram (DIS) formulations.

Article Snippet: DIS powder and 2-hydroxypropyl-β-cyclodextrin (HPCD) were kindly donated by Ouchi Shinko Chemical Industrial Co., Ltd. (Tokyo, Japan) and Nihon Shokuhin Kako Co., Ltd. (Tokyo, Japan), respectively.

Techniques: Purification

Journal: Pharmaceutics

Article Title: Novel Sustained-Release Drug Delivery System for Dry Eye Therapy by Rebamipide Nanoparticles

doi: 10.3390/pharmaceutics12020155

Figure Lengend Snippet: Characterization of the particle size, shape and solubility of rebamipide solid microparticles (REB-MPs) and nanoparticle (REB-NPs)-based ophthalmic formulation. ( A ) REB-MPs size by laser diffraction measurement. ( B ) REB-NPs size by dynamic light scattering measurement. ( C ) AFM image of REB-NPs. ( D ) Drug solubility in REB-MPs and REB-NPs. n = 6. * P < 0.05, vs. REB-MPs. 99.92% of the rebamipide existed in the solid form in REB-NPs, and the mean particle size was 109.5 nm.

Article Snippet: Briefly, rebamipide powder (particle size 741 ± 12.7 nm) purchased from Wako Pure Chemical Industries, Ltd. (Osaka, Japan) was mixed with 2-hydroxypropyl-β-cyclodextrin (HPβCD, Nihon Shokuhin Kako Co., Ltd., Tokyo, Japan) and type SM-4 methylcellulose (MC, Shin-Etsu Chemical Co., Ltd., Tokyo, Japan) in distilled water, and the dispersions were milled at 5500 rpm for 1 min × 30 times using 0.1 mm zirconia beads and a Micro Smash MS-100R (TOMY SEIKO Co. Ltd., Tokyo, Japan).

Techniques: Solubility

Journal: Pharmaceutics

Article Title: Novel Sustained-Release Drug Delivery System for Dry Eye Therapy by Rebamipide Nanoparticles

doi: 10.3390/pharmaceutics12020155

Figure Lengend Snippet: Stability of rebamipide solid in REB-NPs one month after preparation. ( A ) REB-NPs size by dynamic light scattering measurement. ( B ) Number of rebamipide nanoparticles in REB-NPs. ( C ) AFM image of REB-NPs. ( D ) Drug solubility in REB-MPs and REB-NPs. n = 6. The rebamipide solid in REB-NPs remained in the nano-size range, and no difference was observed in either the shape or solubility after one month.

Article Snippet: Briefly, rebamipide powder (particle size 741 ± 12.7 nm) purchased from Wako Pure Chemical Industries, Ltd. (Osaka, Japan) was mixed with 2-hydroxypropyl-β-cyclodextrin (HPβCD, Nihon Shokuhin Kako Co., Ltd., Tokyo, Japan) and type SM-4 methylcellulose (MC, Shin-Etsu Chemical Co., Ltd., Tokyo, Japan) in distilled water, and the dispersions were milled at 5500 rpm for 1 min × 30 times using 0.1 mm zirconia beads and a Micro Smash MS-100R (TOMY SEIKO Co. Ltd., Tokyo, Japan).

Techniques: Solubility

Journal: Pharmaceutics

Article Title: Novel Sustained-Release Drug Delivery System for Dry Eye Therapy by Rebamipide Nanoparticles

doi: 10.3390/pharmaceutics12020155

Figure Lengend Snippet: Rebamipide release from REB-MPs and REB-NPs through 25 nm and 450 nm pore membranes. Drug release from REB-MPs and REB-NPs through ( A ) 25 nm and ( B ) 450 nm pore membranes. ( C ) Particle size and ( D ) number of rebamipide nanoparticles that passed through the 450 nm pore membrane 24 h after the application of REB-NPs. Data show the size distribution and number of nanoparticles in the reservoir chamber. n = 5–6. N.D., not detectable. * P < 0.05, vs. REB-MPs. The rebamipide solid was released as nanoparticles from REB-NPs.

Article Snippet: Briefly, rebamipide powder (particle size 741 ± 12.7 nm) purchased from Wako Pure Chemical Industries, Ltd. (Osaka, Japan) was mixed with 2-hydroxypropyl-β-cyclodextrin (HPβCD, Nihon Shokuhin Kako Co., Ltd., Tokyo, Japan) and type SM-4 methylcellulose (MC, Shin-Etsu Chemical Co., Ltd., Tokyo, Japan) in distilled water, and the dispersions were milled at 5500 rpm for 1 min × 30 times using 0.1 mm zirconia beads and a Micro Smash MS-100R (TOMY SEIKO Co. Ltd., Tokyo, Japan).

Techniques:

Journal: Pharmaceutics

Article Title: Novel Sustained-Release Drug Delivery System for Dry Eye Therapy by Rebamipide Nanoparticles

doi: 10.3390/pharmaceutics12020155

Figure Lengend Snippet: Changes in rebamipide levels in the lacrimal fluid and meibum of rabbits receiving a single treatment of REB-NPs or REB-MPs. ( A ) Rebamipide profile and ( B ) AUC LF in the lacrimal fluid after the application of REB-MPs or REB-NPs. ( C ) Rebamipide levels in the meibum and lacrimal fluid without meibum after the application of REB-MPs or REB-NPs. Here, 20 min and 60 min after the application of REB-NPs, the lacrimal fluid without meibum was collected from the eyelid side using Schirmer tear test strips. n = 5–7. * P < 0.05, vs. REB-MPs for each group. # P < 0.05, vs. lacrimal fluid without meibum for each group. The rebamipide in the REB-NPs penetrated the eyelid, and was delivered to the lacrimal fluid through the meibomian glands.

Article Snippet: Briefly, rebamipide powder (particle size 741 ± 12.7 nm) purchased from Wako Pure Chemical Industries, Ltd. (Osaka, Japan) was mixed with 2-hydroxypropyl-β-cyclodextrin (HPβCD, Nihon Shokuhin Kako Co., Ltd., Tokyo, Japan) and type SM-4 methylcellulose (MC, Shin-Etsu Chemical Co., Ltd., Tokyo, Japan) in distilled water, and the dispersions were milled at 5500 rpm for 1 min × 30 times using 0.1 mm zirconia beads and a Micro Smash MS-100R (TOMY SEIKO Co. Ltd., Tokyo, Japan).

Techniques:

Journal: Pharmaceutics

Article Title: Novel Sustained-Release Drug Delivery System for Dry Eye Therapy by Rebamipide Nanoparticles

doi: 10.3390/pharmaceutics12020155

Figure Lengend Snippet: Drug delivery routes of rebamipide in REB-NPs, and the therapeutic mechanism for dry eye.

Article Snippet: Briefly, rebamipide powder (particle size 741 ± 12.7 nm) purchased from Wako Pure Chemical Industries, Ltd. (Osaka, Japan) was mixed with 2-hydroxypropyl-β-cyclodextrin (HPβCD, Nihon Shokuhin Kako Co., Ltd., Tokyo, Japan) and type SM-4 methylcellulose (MC, Shin-Etsu Chemical Co., Ltd., Tokyo, Japan) in distilled water, and the dispersions were milled at 5500 rpm for 1 min × 30 times using 0.1 mm zirconia beads and a Micro Smash MS-100R (TOMY SEIKO Co. Ltd., Tokyo, Japan).

Techniques:

Journal: British journal of pharmacology

Article Title: Veklury® (remdesivir) formulations inhibit initial membrane-coupled events of SARS-CoV-2 infection due to their sulfobutylether-β-cyclodextrin content.

doi: 10.1111/bph.16063

Figure Lengend Snippet: FIGURE 1 Veklury® (remdesivir) formulations induce alterations in membrane structure and disrupt lipid rafts similarly to cyclodextrins (CDs) in a cholesterol-dependent manner independently of remdesivir. (a) Control HEK/ACE2 + TMPRSS2 cells and those treated with 1-, 5- or 10-mM MβCD, HPβCD, SBECD, Veklury® P (powder) or Veklury® S (solution), 100-μM remdesivir (REM) or 200-μM cholesterol (CHOL) were labelled with cholera toxin subunit B (CTX-B), a lipid raft marker, and N-[3-(40-dihexylamino-3-hydroxy-flavonyl-6-oxy)-propyl]N,N-dimethyl-N- (3-sulfopropyl)-ammonium inner salt (F66), an environment-sensitive fluorescent indicator. Representative confocal microscopic images taken from the flat, bottom membrane region adjacent to the coverslip show F66 intensities of the normal (N*) and tautomeric (T*) excited states and the T*/N* emission ratios calculated pixel by pixel. Cell membrane masks selected manually in CTX-B images were segmented using the maxentropy algorithm to ‘raft’ (CTX-B high) and ‘non-raft’ (CTX-B low) regions corresponding to high and low intensities of the raft markers, respectively, and average T*/N* intensity ratios were determined separately for the two masks (symbols in [c]). (b) Pixelwise distributions of the T*/N* F66 emission ratio in CTX-B high ‘raft’ and CTX-B low ‘non-raft’ regions of control cells are displayed. As an alternative definition for raft regions, a threshold value of the T*/N* ratio was determined (red dashed line) and membrane pixels were considered as ‘raft’ and ‘non-raft’ regions when being above and below the threshold, respectively (evaluation shown by the bars in [c]). The threshold value was chosen to result in a segmentation pattern similar to that obtained in (a). (c) The average F66 T*/N* ratios calculated for CTX-B high ‘raft’ and CTX-B low ‘non-raft’ pixels (circles and squares, respectively; numerical values to be read on the left vertical axis) as well as the relative fraction of ‘raft’ pixels (bars, numerical values to be read on the right vertical axis) above the F66 emission ratio threshold (shown by the red line in [b]) were determined in individual cells (n = 20) and the mean ± SD values are plotted. Asterisks indicate significant differences compared to the control samples (*P < 0.05; one-way ANOVA followed by Tukey's HSD test). See details of statistical analysis in Table S1.

Article Snippet: Conclusion and Implications: Our findings call for the differentiation of Veklury® for- mulations in meta-analyses of clinical trials, potentially revealing neglected benefits Abbreviations: CD, cyclodextrin; CHOL, cholesterol complexed with MβCD; CTX-B, cholera toxin subunit B; Delta, B.1.617.2 variant strain of SARS-CoV-2; F66, N-[3-(40-dihexylamino3-hydroxy-flavonyl-6-oxy)-propyl]N,N-dimethyl-N-(3-sulfopropyl)-ammonium inner salt; HPβCD, hydroxypropyl-β-cyclodextrin; MβCD, methyl-β-cyclodextrin; N*, normal excited state of F66; Omicron, B.1.1.529 Ba1 variant strain of SARS-CoV-2; RBD, receptor-binding domain; REM, remdesivir (GS-5734) in DMSO; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; SBECD, sulfobutylether-β-cyclodextrin; T*, tautomeric excited state of F66; Veklury® P, powder formulation of Veklury® (remdesivir), Veklury® S, solution formulation of Veklury® (remdesivir); WT, Wuhan-Hu-1 strain of SARS-CoV-2.

Techniques: Membrane, Control, Marker

Journal: British journal of pharmacology

Article Title: Veklury® (remdesivir) formulations inhibit initial membrane-coupled events of SARS-CoV-2 infection due to their sulfobutylether-β-cyclodextrin content.

doi: 10.1111/bph.16063

Figure Lengend Snippet: FIGURE 6 Veklury® (remdesivir) formulations effectively decrease ACE2 binding of Omicron SARS-CoV-2 spike receptor-binding domain (RBD) and the cellular uptake of Omicron SARS-CoV-2 spike trimer due to their SBECD content. (a) HEK/ACE2 + TMPRSS2 (left panel) or Calu-3 cells (right panel) were treated with SBECD, Veklury® P (powder) or Veklury® S (solution) at CD concentrations of 1, 5 and 10 mM. Then, HEK/ ACE2 + TMPRSS2 cells were incubated in the presence of 0.2-μgml1 Omicron SARS-CoV-2 spike RBD–GFP, whereas Calu-3 cells were labelled with 1-μgml1 Omicron RBD–GFP for 4 min. The emitted fluorescence intensities of individual cells were subsequently measured using flow cytometry, and the mean intensity was calculated from data of at least 10,000 cells of normal morphology per sample. The average values of six independent measurements (±SD) were calculated, normalized to the mean value determined in untreated control samples and plotted as a function of the applied concentrations of CD. Asterisks indicate significant differences of samples treated with the highest applied concentrations compared to the control samples (*P < 0.05; two-way ANOVA followed by Tukey's HSD test). See details of statistical analysis in Table S6. (b) HEK/ACE2 + TMPRSS2 (left panel) or Calu-3 cells (right panel) treated with SBECD, Veklury® P or Veklury® S at CD concentrations of 1 and 5 mM for 1 h were subsequently incubated for 4 h in the presence of Omicron SARS-CoV-2 spike trimers conjugated with Alexa Fluor 488. The average fluorescence intensity values emitted by Alexa Fluor 488-labelled trimers were calculated using data of intracellular pixels identified using the membrane marker N-[3-(40-dihexylamino-3-hydroxy-flavonyl-6-oxy)-propyl]N,N-dimethyl-N-(3-sulfopropyl)-ammonium inner salt (F66) as described in Figure 5 for individual cells, which were subsequently normalized to the median value determined in untreated control samples. The number of cells obtained from five independent experiments and involved in the analysis was from left to right: 382, 348, 373, 396, 388, 402 and 393 for Omicron trimer uptake in HEK/ACE2 + TMPRSS2 and 308, 250, 256, 223, 222, 232 and 296 for Omicron trimer uptake in Calu-3. Data points indicated in the figure were obtained from individual cells and plotted along with median values with quartiles. Grey shaded areas show ranges between 0.5 and 1. Asterisks indicate significant differences compared to the control samples (*P < 0.05; one-way ANOVA followed by Tukey's HSD test). See details of statistical analysis in Table S6.

Article Snippet: Conclusion and Implications: Our findings call for the differentiation of Veklury® for- mulations in meta-analyses of clinical trials, potentially revealing neglected benefits Abbreviations: CD, cyclodextrin; CHOL, cholesterol complexed with MβCD; CTX-B, cholera toxin subunit B; Delta, B.1.617.2 variant strain of SARS-CoV-2; F66, N-[3-(40-dihexylamino3-hydroxy-flavonyl-6-oxy)-propyl]N,N-dimethyl-N-(3-sulfopropyl)-ammonium inner salt; HPβCD, hydroxypropyl-β-cyclodextrin; MβCD, methyl-β-cyclodextrin; N*, normal excited state of F66; Omicron, B.1.1.529 Ba1 variant strain of SARS-CoV-2; RBD, receptor-binding domain; REM, remdesivir (GS-5734) in DMSO; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; SBECD, sulfobutylether-β-cyclodextrin; T*, tautomeric excited state of F66; Veklury® P, powder formulation of Veklury® (remdesivir), Veklury® S, solution formulation of Veklury® (remdesivir); WT, Wuhan-Hu-1 strain of SARS-CoV-2.

Techniques: Binding Assay, Incubation, Fluorescence, Flow Cytometry, Control, Membrane, Marker