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Graphical abstract Abstract The aim of this study is to improve the bioavailability of ticagrelor, BCS class 4 drug, using solid dispersion technique, and to evaluate the potential of ticagrelor loaded-solid dispersion, as a new formulation. The solid dispersion formulation was prepared via solvent evaporation method using ethanol. TPGS and Neusilin® US2 selected via screening studies were used for preparing formulation. The results of scanning electron microscopy, differential scanning calorimetry and powder X-ray diffraction showed that the crystallinity of the ticagrelor was completely transformed to an amorphous form and maintained in the solid dispersion formulation. The released amount of the optimized solid dispersion significantly increased by 2.2- and 34-fold in comparison with physical mixture (Ticagrelor:TPGS:Neusilin® US2 = 1:2:2, w/w/w) and commercial product (Brilinta®) in distilled water at 90 min, respectively. The absorptive permeability was improved (1.4-fold) and the efflux ratio was decreased (0.45-fold) by formulation containing TPGS acting as a P-gp inhibitor compared to pure drug. The solid dispersion formulation improved the peak plasma concentration (C max) and relative bioavailability compared to that of pure drug as 238.09 ± 25.96% and 219.78 ± 36.33%, respectively, after oral administration in rats. Thus, we successfully prepared the solid dispersion formulation for enhancing oral bioavailability of ticagrelor, and then this formulation would be recommended as a practical oral pharmaceutical product. [ABSTRACT FROM AUTHOR]

Polyacrylonitrile (PAN) fiber was metallized by nickel-phosphorus (Ni-P) in an electroless plating process. Firstly, the surface of PAN fiber was activated by palladium (Pd) nanocatalysts by using a drying process in which palladium(II) bis(acetylacetonate), Pd(acac) 2 was spontaneously reduced to Pd nanocatalysts in180 °C N 2 atmosphere without using any reducing agent. And then Ni-P alloy was coated on the Pd activated PAN fiber in an electroless Ni-P plating solution without using SnCl 2 -sensitizing solution. The morphology was observed by scanning electron microscopy (SEM) and elemental analyses were carried out by energy dispersive spectroscopy (EDS) and X-ray photoelectron spectroscopy (XPS). The composition ratio of Ni: P was 85.3: 14.7 atomic % and the growth rate of Ni-P layer decreased with increasing plating time. The thickness of Ni-P plating layers for 10, 30 and 60 min were 0.64, 1.03 and 1.22 μm, respectively. Electromagnetic interference shielding effectiveness (EMI-SE) of Ni-P plated PAN fiber (50 wt%)/epoxy composite was more than 30 dB in the frequency range from 30 MHz to 1500 MHz. [ABSTRACT FROM AUTHOR]

Abstract: Platycodin D (PD) is the major triterpene saponin in the root of Platycodon grandiflorum. The aim of the present study was to evaluate the protective effects of PD on bile duct ligation (BDL)-induced cholestasis in mice. Mice were allocated to five groups: sham, BDL alone, and BDL with PD treatment at 1, 2, and 4mg/kg. PD was administered to the mice for 28 consecutive days after the BDL operation. PD treatment of BDL-operated mice decreased serum alanine aminotransferase, serum aspartate aminotransferase, and total bilirubin levels by up to 37%, 31%, and 41%, respectively, in comparison with the levels in mice that underwent BDL alone. PD treatment attenuated oxidative stress, as evidenced by an increase in anti-oxidative enzyme levels glutathione and superoxide dismutase together with a decrease in lipid peroxidation and oxidative stress indices levels of malondialdehyde and nitric oxide. Histopathological studies further confirmed the protective effects of PD on cholestasis-induced hepatic injury and liver fibrosis in mice. In addition, nuclear factor-kappa B and inducible nitric oxide synthase levels significantly decreased after PD treatment, as did the levels of hepatocyte apoptosis. Taken together, these results suggest that PD treatment might be beneficial in cholestasis-induced hepatotoxicity. [Copyright &y& Elsevier]

Context: The root of Platycodon grandiflorum (Jacq.) A. DC. (Campanulaceae) has been widely studied for its hepatoprotective effects against various hepatotoxicants. Objective: The present study evaluated the protective effect of the standardized aqueous extract of P. grandiflorum (BC703) on cholestasis-induced hepatic injury in mice. Materials and methods: BC703 is a standardized aqueous extract of P. grandiflorum in reference to platycodin D (at least 0.8%). The mice were allocated into five groups as follows: Sham-operated, bile duct ligation (BDL) alone, and BDL with BC703 (1, 5, and 10 mg/kg BW) treated group. BC703 was given for 3 consecutive days before BDL operation. The animals were sacrificed by CO2 anesthesia post-24 h of BDL operations. Results and discussion: Serum alanine aminotransferase and serum aspartate aminotransferase increased to 395.2 ± 90.0 and 266.0 ± 45.6 Unit/L in the BDL alone group and decreased with BC703 in a dose-dependent manner. Especially the 10 mg/kg of BC703-treated mice showed a 77% decrease of serum alanine aminotransferase and 56% of aspartate aminotransferase as compared with BDL alone. Decreased antioxidant enzyme levels in BDL alone group were elevated in BC703-treated groups ranging from 7 to 29% for glutathione and from 13 to 25% for superoxide dismutase. BC703 treatment also attenuated malondialdehyde (from 3 to 32%) and nitric oxide levels (from 32 to 50%) as compared with BDL alone. Histopathological studies further confirmed the hepatoprotective effect of BC703 in BDL-induced cholestesis. Conclusion: BC703 could attenuate liver injury by BDL in mice, and test results indicate that BC703 might be useful in cholestatic liver injury. [ABSTRACT FROM AUTHOR]

The optimum amount of Sr in La1−xSrxMnO3 for solid oxide fuel cell (SOFC) cathode material was studied by observing the charge transfer resistance, electrical conductivity, and reactivity with the electrolyte. Three transition metals (Cr, Mn and Co) were substituted to the B site of La0.5Sr0.5BO3 and the electrochemical characteristics were investigated by AC impedance method. The electrical conductivity and interface resistance decreased as the amount of Sr increased and the lowest value was shown when the amount of Sr was 50 mol%. The reactivity between the electrolyte and La1−xSrxBO3 (B=Cr, Mn, Co) was investigated and it was found that the secondary phase, La2Zr2O7, was not formed when the substitution amount of Sr was 50 mol%. The activation energy of the electrode was 1.186, 1.761, and 2.043 eV for La0.5Sr0.5BO3 (B=Cr, Mn, and Co, respectively). The calculated capacitance value of La0.5Sr0.5MnO3 was 3.23×103 μF, so the three-phase boundary (TPB) of this electrode was broader than the other electrodes. Consequently the La0.5Sr0.5MnO3 electrode is appropriate as a cathode material for SOFC due to its broad electrochemical reaction site and its electrochemical characteristics. [Copyright &y& Elsevier]

Zinc oxide (ZnO) nanorods with hexagonal morphology were grown on the surface of polyacrylonitrile (PAN) fiber, in which PAN fiber was pre-activated by Pd nanoparticles via a spontaneous reduction of palladium(II) bis(acetylacetonate), Pd(acac) 2 at 180°C under nitrogen atmosphere. The length of the ZnO nanorod was 13.0 μm having wurtzite cryatal structure. • A drying process to activate the surface of PAN fiber with Pd nanoparticles. • ZnO nanorods grown on the Pd-activated PAN surface. • 13.0 μm long ZnO nanorods having wurtzite crystalline structure consisted of hexagonal lattice. • H 2 S uptake amount of ZnO nanorods was 12.4 wt%. Zinc oxide (ZnO) nanorods were synthesized on the surface of polyacrylonitrile (PAN) fiber by electroless reaction, which was pre-activated with palladium (Pd) nanoparticles. Pd-activation process was achieved by a reduction reaction of palladium(II) bis(acetylacetonate), Pd(acac) 2 in a dry process, that is to say, Pd(acac) 2 molecules sublimated, penetrated into the surface of PAN fiber and spontaneously reduced to Pd nanoparticles at 180 °C under nitrogen atmosphere. The morphology of hexagonal ZnO nanorods grown on the surface of PAN fiber was observed by a field emission scanning electron microscopy (FE-SEM) and their elemental composition was evaluated by an X-ray photoelectron spectroscopy (XPS). X-ray diffraction (XRD) analysis showed that the crystalline structure of ZnO nanorods was wurtzite cryatal structure consisted of hexagonal lattice. Sulfur removal performance of the ZnO nanorod increased with increasing electroless reaction time. The saturated H 2 S uptake weight was 12.4 wt% of ZnO/PAN fiber prepared at 80 °C for 180 min. [ABSTRACT FROM AUTHOR]

Cobalt or nickel/cobalt on carbon nanotube (Co@CNT, NiCo@CNT) catalysts were synthesized by heat treatment of the metal-organic framework, ZIF-67. The X-ray patterns of the synthesized ZIF-67 and the catalysts confirmed their crystalline structures. The field-emission scanning electron microscopy (FESEM) images of ZIF-67 after pyrolysis showed that the dodecahedral crystalline structure of ZIF-67 was retained, and the organic ligands were converted into CNTs and graphitic carbon in an H 2 gas environment. The transmission electron microscopy images of the synthesized catalysts confirm the presence of the Ni or Co atoms at the tips of the carbon nanotubes. The NiCo@CNT catalyst exhibited a higher surface area and larger pore volume than those of Co@CNT. X-ray photoelectron spectroscopy confirmed the presence of pyridinic nitrogen, which forms Co-N x and Ni-N x, active groups. In anion exchange membrane-unitized regenerative fuel cells (AEM-URFC), NiCo@CNT as a bifunctional oxygen electrode (BOE) catalyst showed a higher current density and lower Tafel slope compared to that of Co@CNT. The cell with the NiCo@CNT catalyst in BOE exhibits the highest current density of 130.0 mA cm−2 at 0.3 V (fuel cell mode) and 32.5 mA cm−2 at 2.0 V (water electrolyzer mode) among all catalysts. This cell exhibited a maximum 38.90 % round trip efficiency, which was comparable to that of the benchmark noble metal (Ir-black) catalyst (38.40 %). [Display omitted] • Preparation of MOF from transition metals and organic ligands by hydrothermal process. • Metal encapsulated in carbon nanotube electrocatalysts synthesis from ZIF-67. • Preparation of working electrode to detect the electrocatalytic performance of the catalysts. • Bifunctional activity evaluation of the prepared catalysts on AEM-URFC oxygen electrode. [ABSTRACT FROM AUTHOR]

Simple Summary: Despite the proven efficacy and confirmed safety of dendritic cell therapy, the limited response against cancer remains a challenge. This study aimed to investigate the potential of combinational tumor-associated antigens (TAAs) pulsing to enhance the antigen-presenting ability of dendritic cells. TAAs-pulsed DCs demonstrated anti-cancer capabilities, including tumor growth suppression, increased proliferation of splenic T cells, and elevated IFN-γ secretion. While the combinational pulsing approach shows promise in addressing the limitations of dendritic cell therapies, additional research is required to explore diverse combinations of TAAs for potential therapeutic applications. NSCLC, the most common type of lung cancer, is often diagnosed late due to minimal early symptoms. Its high risk of recurrence or metastasis post-chemotherapy makes DC-based immunotherapy a promising strategy, offering targeted cancer destruction, low side effects, memory formation, and overcoming the immune evasive ability of cancers. However, the limited response to DCs pulsed with single antigens remains a significant challenge. To overcome this, we enhanced DC antigen presentation by pulsing with TAAs. Our study focused on enhancing DC-mediated immune response specificity and intensity by combinatorial pulsing of TAAs, selected for their prevalence in NSCLC. We selected four types of TAAs expressed in NSCLC and pulsed DCs with the optimal combination. Next, we administered TAAs-pulsed DCs into the LLC1 mouse model to evaluate their anti-tumor efficacy. Our results showed that TAAs-pulsed DCs significantly reduced tumor size and promoted apoptosis in tumor tissue. Moreover, TAAs-pulsed DCs significantly increased total T cells in the spleen compared to the unpulsed DCs. Additionally, in vitro stimulation of splenocytes from the TAAs-pulsed DCs showed notable T-cell proliferation and increased IFN-γ secretion. Our findings demonstrate the potential of multiple TAA pulsing to enhance the antigen-presenting capacity of DCs, thereby strengthening the immune response against tumors. [ABSTRACT FROM AUTHOR]

Anion exchange membranes (AEMs) play a critical role in anion exchange membrane-unitized regenerative fuel cells (AEM-URFCs). In this study, we investigated the effect of different membrane treatment processes on the performance of AEM-URFCs. By replacing bromide ions (Br−) with hydroxyl ions (OH−), we were able to greatly enhance cell performance. We treated a membrane electrode assembly (MEA) with KOH solutions of varying solvents and concentrations, which caused the AEM to swell and replace Br− ions with OH− ions. We found that the concentration of OH− ions in the KOH solution had a significant impact on Br− ion replacement. The MEA treated with 1.0 M KOH in a mixture of isopropyl alcohol (IPA) and deionized water (H2O) (25/75 vol%) had the lowest Br− ion content and exhibited a current density of 215.0 mA cm−2 at 0.5 V (fuel cell mode) and 65.0 mA cm−2 at 2.0 V (water electrolyzer mode). These findings can inform future research on AEM-based fuel cells and water electrolyzers by identifying an optimal membrane pretreatment process. [ABSTRACT FROM AUTHOR]

[Display omitted] Baicalin, a glucuronic flavone, is the major active component in the medicinal plant Scutellaria baicalensis. Herein, baicalin was irradiated by γ-rays to afford four unusual flavanones, baicalinols A (2), B (3), and C (4) and peroxybaicaleinol (5), and two known flavones, oroxylin A (6) and baicalein (7). The structures of the hydroxymethylated products were elucidated using nuclear magnetic resonance spectroscopy and mass spectrometry, and their absolute configuration was established using electronic circular dichroism spectroscopy. Novel hydroxymethylated flavanones 2 and 3 suppressed both nitric oxide (NO) production and the expression of inducible NO synthase and showed significantly higher anti-inflammatory activities in lipopolysaccharide-stimulated macrophages than the parent compound. These newly generated hydroxymethylated flavanones can be potentially used for treating inflammatory diseases. [ABSTRACT FROM AUTHOR]

Background: Urine-derived stem cells (UDSCs) can be easily isolated from urine and possess excellent stem cell characteristics, making them a promising source for cell therapeutics. Due to their kidney origin specificity, UDSCs are considered a superior therapeutic alternative for kidney diseases compared to other stem cells. To enhance the therapeutic potential of UDSCs, we developed a culture method that effectively boosts the expression of Klotho, a kidney-protective therapeutic factor. We also optimized the Good Manufacturing Practice (GMP) system to ensure stable and large-scale production of clinical-grade UDSCs from patient urine. In this study, we evaluated the in vivo safety and distribution of Klotho-enhanced UDSCs after intravenous administration in accordance with Good Laboratory Practice (GLP) regulations. Methods: Mortality and general symptoms were continuously monitored throughout the entire examination period. We evaluated the potential toxicity of UDSCs according to the administration dosage and frequency using clinical pathological and histopathological analyses. We quantitatively assessed the in vivo distribution and retention period of UDSCs in major organs after single and repeated administration using human Alu-based qPCR analysis. We also conducted long-term monitoring for 26 weeks to assess the potential tumorigenicity. Results: Klotho-enhanced UDSCs exhibited excellent homing potential, and recovered Klotho expression in injured renal tissue. Toxicologically harmful effects were not observed in all mice after a single administration of UDSCs. It was also verified that repeated administration of UDSCs did not induce significant toxicological or immunological adverse effects in all mice. Single and repeated administrated UDSCs persisted in the blood and major organs for approximately 3 days and cleared in most organs, except the lungs, within 2 weeks. UDSCs that remained in the lungs were cleared out in approximately 4–5 weeks. There were no significant differences according to the variation of sex and administration frequency. The tumors were found in the intravenous administration group but they were confirmed to be non-human origin. Based on these results, it was clarified that UDSCs have no tumorigenic potential. Conclusions: Our results demonstrate that Klotho-enhanced UDSCs can be manufactured as cell therapeutics through an optimized GMP procedure, and they can be safely administered without causing toxicity and tumorigenicity. [ABSTRACT FROM AUTHOR]

Radiation molecularly transforms naturally occurring products by inducing the methoxylation, hydroxylation, and alkylation of parent compounds, thereby affecting the anti-inflammatory capacities of those compounds. Minaprine (1) modified by ionizing radiation generated the novel hydroxymethylation hydropyridazine (2), and its chemical structure was determined based on NMR and HRESIMS spectra. Compared to the original minaprine, the novel generated product showed a highly enhanced anti-inflammatory capacity inhibited nitric oxide (NO) and prostaglandin E2 (PGE2) production in lipopolysaccharide (LPS)-stimulated RAW 264.7 and DH82 macrophage cells. In addition, minaprinol (2) effectively inhibited cyclooxygenase-2 (COX-2) and inducible NO synthase (iNOS) at the protein level and pro-inflammatory cytokine (tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and IL-10) production in macrophages. [ABSTRACT FROM AUTHOR]

Phenylethyl resorcinol (PR) has been known to allow the whitening effect by inhibiting formation of tyrosinase. PR has solubility of 4.05 ± 0.02 mg/g for water and log P of 3.017, proposed an amphiphilic substance. Hybrid PLGA microspheres with oil (HPMSs) have been used to improve encapsulation efficiency (EE) of hydrophilic molecules and control the release of them. The solubility (618.3 ± 22.29 mg/g) of PR was the highest in CapryolTM 90. The formulations (F6 and F'6) were selected after evaluation with EE and the released % (w/w) at 8 h. HPMSs showed 40% (w/w) increase of EE compared to that in CPMSs. Retention study on rat skin at 12 h resulted in that PR of HPMSs was remained more than that of CPMSs in dermal layer forming the melanin. HPMSs showed 1.4-fold increase of tyrosinase inhibition significantly in melanoma cells than that of the PR solution at 24 h. [ABSTRACT FROM AUTHOR]

In this study, noble metal-free Co(OH)F and CoP nanorod electrocatalysts were prepared and explored as bifunctional oxygen electrodes (BOE) in anion exchange membrane-unitized regenerative fuel cells (AEM-URFCs). A CoP nanorod was synthesized from Co(OH)F via the hydrothermal treatment of cobalt nitrate, ammonium fluoride, and urea, followed by phosphorization. The crystal structures, surface morphologies, pore distributions, and elemental statuses of the obtained catalysts were analyzed to identify the changes caused by the incorporation of fluorine and phosphorus. The presence of F and P was confirmed through EDS and XPS analyses, respectively. Using these catalysts, the AEM-based URFCs were operated with hydrogen and oxygen in the fuel cell mode and pure water in the electrolysis mode. In addition, the electrocatalytic activities of the catalysts were evaluated using cyclic voltammetry and electrochemical impedance spectroscopy. In the AEM-URFC test, the CoP catalyst in the BOE delivered the best performance in the fuel cell mode (105 mA cm−2 at 0.3 V), and Co(OH)F was suitable for the water electrolyzer mode (30 mA cm−2 at 2.0 V). CoP and Co(OH)F exhibited higher round trip efficiency (RTE) and power densities than the conventional Co3O4 catalyst. [ABSTRACT FROM AUTHOR]

Low-intensity ultrasound (LIUS) enhances the proliferation rate of various mammalian stem cells through mechanical stimulation. This study quantitively finds suitable LIUS stimulation parameters for increasing the proliferation rate of human adipose-derived mesenchymal stem cells (hAdMSCs) for mass production. Various stimulation conditions of LIUS were assessed based on the beam pattern of the ultrasonic transducer and the attenuation of the sound waves. Using optimal LIUS stimulation parameters for enhancing proliferation of hAdMSCs taken from bromodeoxyuridine (BrdU) incorporation assay, long-term culture of hAdMSCs was performed for 16 days. The resultant hAdMSCs were characterized for various biomarkers such as CD34−, CD45−, CD73+, CD95+, CD105+ and cytological staining and a cytokine array assay. LIUS stimulation parameters found for enhancing the hAdMSCs proliferation were the frequency of 5 MHz, an intensity of 300 mWcm−2, a duration of 10 min per day, and continuous waves with a 100% duty cycle. The LIUS stimulated hAdMSCs group showed a 3.25-fold increase in the cell number compared to the control group after 16 days of culture. By confirming the effects of quantitatively measured LIUS stimulation on the enhancement of hAdMSCs proliferation, this study may be a foundation for the applications of LIUS stimulation in the industrial-scale production of hAdMSCs. [ABSTRACT FROM AUTHOR]

Grapiprant, a novel pharmacologically active ingredient, acts as a selective EP4 receptor antagonist whose physiological ligand is prostaglandin E2 (PGE2). It is currently under development for use in humans and dogs for the control of pain and inflammation associated with osteoarthritis. The aim of the present study was to develop an easy and sensitive method to quantify grapiprant in canine plasma and to apply the method in a canine patient. Several parameters, both in the extraction and detection method were evaluated. The final mobile phase consisted of ACN:AcONH 4 (20 mM) solution, pH 4 (70:30, v/v) at a flow rate of 1 mL/min. The elution of grapiprant and IS (metoclopramide) was carried out in isocratic mode through a Synergi Polar-RP 80A analytical column (150 mm × 4.6 mm). The best excitation and emission wavelengths were 320 and 365 nm, respectively. Grapiprant was extracted from the plasma using CHCl 3 , which gave a recovery of 88.1 ± 10.22% and a lower limit of quantification (LLOQ) of 10 ng/mL. The method was validated in terms of linearity, limit of detection (LOD), LLOQ, selectivity, accuracy and precision, extraction recovery, stability, and inter-laboratory cross validation, according to international guidelines. The chromatographic runs were specific with no interfering peaks at the retention times of the analyte and IS, as confirmed by HPLC-MS experiments. In conclusion, this was a simple and effective method using HPLC-FL to detect grapiprant in plasma, which may be useful for future pharmacokinetic studies. [ABSTRACT FROM AUTHOR]

Metamizole (MT) is an analgesic and antipyretic drug labelled for use in humans, horses, cattle, swine, and dogs. MT is rapidly hydrolysed to the primary metabolite 4-methylaminoantipyrine (MAA). MAA is formed in much larger amounts compared to other minor metabolites, and it has been selected from the regulatory European Medicines Agency as a marker residue for MRL calculation. The aim of this research was to evaluate the pharmacokinetic profiles of MAA after 20 mg/kg MT by intravenous (IV) and intramuscular (IM) administrations in healthy sheep. Twelve sheep were randomly allocated to two equal treatment groups according to a 2 × 2 crossover study. Blood was collected at predetermined times within 36 h and plasma was analysed by a validated HPLC UV method. No behavioural changes or alterations in health parameters were observed in the IV or IM groups of animals during or after (up to 7 days) the drug administration. Plasma concentrations of MAA after IV administration of MT were detectable from 5 min to 8 h in all the sheep, they were still detectable at 10 h in two animals, and the plasma quantification of MAA was possible from 5 min to 10 h in all the animals after IM administration. The only two significantly different parameters between the groups were maximum concentration ( C max ) and time to maximum concentration ( T max ) ( P < 0.01). The AUC IM /AUC IV was 1.12. The present study showed that no clinically relevant difference in the MAA was found after IM and IV administration of MT. Further studies are now necessary to assess the safety and efficacy profile of MT in sheep. [ABSTRACT FROM AUTHOR]

The application of heteroatom doped cobalt (Ni@Co/C) prepared from a porous metal–organic framework as the cathode material for the rechargeable zinc–air batteries has been demonstrated. The Ni@Co/C‐modified electrode showed an excellent catalytic activity toward oxidation–reduction reaction and oxygen evolution reactions. The Co/C catalysts, which were Co particle impregnated on graphitic carbon powders, were synthesized after the calcination of Co3 (SDA)3(DMF)2 precursor, and then Ni deposition (Ni@Co/C) was followed on it by chemical reduction. Linear sweep voltammetry measurement indicates that Ni@Co/C‐H800, which had Ni particles on Co/C derived from MOF at 800 °C under N2, exhibited excellent performance. The stable charging/discharging profiles at 20 mA cm−2 of current were obtained for the 350 h in alkaline medium, suggesting Ni@Co/C‐H800 as a potential candidate for oxidation–reduction and evolution reactions. [ABSTRACT FROM AUTHOR]

Renal fibrosis is an irreversible and progressive process that causes severe dysfunction in chronic kidney disease (CKD). The progression of CKD stages is highly associated with a gradual reduction in serum Klotho levels. We focused on Klotho protein as a key therapeutic factor against CKD. Urine-derived stem cells (UDSCs) have been identified as a novel stem cell source for kidney regeneration and CKD treatment because of their kidney tissue-specific origin. However, the relationship between UDSCs and Klotho in the kidneys is not yet known. In this study, we discovered that UDSCs were stem cells that expressed Klotho protein more strongly than other mesenchymal stem cells (MSCs). UDSCs also suppressed fibrosis by inhibiting transforming growth factor (TGF)-β in HK-2 human renal proximal tubule cells in an in vitro model. Klotho siRNA silencing reduced the TGF-inhibiting ability of UDSCs. Here, we suggest an alternative cell source that can overcome the limitations of MSCs through the synergetic effect of the origin specificity of UDSCs and the anti-fibrotic effect of Klotho. [ABSTRACT FROM AUTHOR]

Abstract: Platycodin D (PD) is well known as a potent triterpenoid saponin having various pharmacological activities isolated from the root of Platycodon grandiflorum (Jacq.) A. DC. (Campanulaceae). We aimed to evaluate protective effect of PD on cisplatin (CDDP)-induced nephrotoxicity. Male ICR mice were allocated into five groups as follows: Negative control, CDDP alone and CDDP with PD (0.1, 1 and 5mg/kg) treated group. PD was given for three consecutive days before CDDP injection. Increased blood urea nitrogen (BUN) and creatinine (CRE) levels in CDDP alone treated mice were decreased to normal range by pretreatment with PD. It also decreased nitric oxide (NO) and lipid peroxidation with increased antioxidant enzymes such as glutathione (GSH), glutathione peroxidase (GPx) and superoxide dismutase (SOD) in PD pretreated mice. In histopathological examination, pretreatment with PD showed ameliorated renal injury such as intraluminal cast formation and epithelial desquamation. Furthermore, over-expression of nuclear factor-kappa B p65 and apoptotic cells were suppressed by PD pretreatment. Taken together, PD pretreatment might be beneficial to CDDP-induced nephrotoxicity. [Copyright &y& Elsevier]

Docetaxel (DTX) has clinical efficacy in the treatment of breast cancer, but it is difficult to develop a product for oral administration, due to low solubility and permeability. This study focused on preparing a self-microemulsifying drug delivery system (SME) loaded with DTX-phospholipid complex (DTX@PLC), to improve the dissolution and gastrointestinal (GI) permeability of DTX. A dual technique combining the phospholipid complexation and SME formulation described as improving upon the disadvantages of DTX has been proposed. We hypothesized that the complexation of DTX with phospholipids can improve the lipophilicity of DTX, thereby increasing the affinity of the drug to the cell lipid membrane, and simultaneously improving permeability through the GI barrier. Meanwhile, DTX@PLC-loaded SME (DTX@PLC-SME) increases the dissolution and surface area of DTX by forming a microemulsion in the intestinal fluid, providing sufficient opportunity for the drug to contact the GI membrane. First, we prepared DTX@PLC-SME by combining dual technologies, which are advantages for oral absorption. Next, we optimized DTX@PLC-SME with nanosized droplets (117.1 nm), low precipitation (8.9%), and high solubility (33.0 mg/g), which formed a homogeneous microemulsion in the aqueous phase. Dissolution and cellular uptake studies demonstrated that DTX@PLC-SME showed 5.6-fold higher dissolution and 2.3-fold higher DTX uptake in Caco-2 cells than raw material. In addition, an ex vivo gut sac study confirmed that DTX@PLC-SME improved GI permeability of DTX by 2.6-fold compared to raw material. These results suggested that DTX@PLC-SME can significantly overcome the disadvantages of anticancer agents, such as low solubility and permeability. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to elucidate the distribution of the columellar artery (CoA) in the mobile nasal septum by means of detailed dissection and histological observation. Methods: Fifteen Korean cadavers were examined; five specimens were dissected to observe the ramification pattern of the CoA from the superior labial artery (SLA), and the noses of ten specimens were quick-frozen in isopropanol cooled with liquid nitrogen and then cryosectioned at a thickness of 40 μm. Results: The arterial vasculature of the CoA in the columella was supplied by the SLA and entered the columella via the columellolabial junction. The vessels of the CoA proceeded anteriorly, inferior to the medial crus of the lower lateral cartilage (MC) at the midline, at the basal and posterior portions of the septum. The vessels traveled closer to the MC than the epidermis. There were very few vessels in the area between the left and right MCs, which was usually packed only with loose connective tissue. More anteriorly, there were more abundant vessels between the MC and the epidermis, with a dispersed distribution. In axial sections, multiple vessels were dispersed in front of the MC, with the pattern varying among the specimens. Furthermore, tiny vessels were also detected in the vicinity of the septal cartilage posterior to the MC. The microdistribution near to the MC was almost consistent. Conclusion: The anatomical findings of the CoA in this study will be useful for safe manipulations during various medical interventions in the columella. [ABSTRACT FROM AUTHOR]

A new series of partially fluorinated and sulfonated poly(biphenylsulfone ketone) block copolymers as proton exchange membrane materials were prepared from hydrophilic and hydrophobic oligomers. The copolymers were characterized by proton NMR, FT-IR, GPC, thermogravimetric analysis (TGA), and differential scanning calorimetry (DSC) thermograms. The membranes showed excellent thermal and oxidative stability; e.g., TGA and DSC demonstrated that all sulfonated block copolymers exhibited good thermal stability with an initial weight loss at temperatures above 200 °C. Block-30 membranes showed low water uptake and acceptable ionic exchange capacity (IEC). The proton conductivity of the block-30 was 75 mS cm−1 at 90 °C and 100% relative humidity (RH), while Nafion-117 had a value of 98 mS cm−1 under the same conditions. AFM analysis of the Block-30 clearly showed that the morphology of the membranes separated the hydrophilic and hydrophobic domains which provided an effective proton-transport pathway. [ABSTRACT FROM AUTHOR]

Abstract: Bipolar plates are major components of fuel cell (FC) stacks and they make up a large portion of the stack volume and cost. In order to reduce their weight and fabrication cost, polymer composite materials with various carbon conducting fillers are tested for use as composite bipolar plates for FCs. The composite materials are prepared by using graphite with a small vol.% of carbon black (CB), multi-walled carbon nanotubes (MWNTs) or carbon fibres (CF) in an epoxy resin. The electrical conductivity and flexural properties of the composites are measured as a function of the carbon conductive filler content. The highest electrical conductivity is observed at a total conducting filler content of 75vol.%. The addition of a small amount of hybrid conducting filler enhances the electrical conductivity up to certain threshold, viz. 5vol.% of CB, 2vol.% of MWNTs, and 7vol.% of CF. Above these thresholds, the electric conductivity decreases with increasing filler content, due to the lack of sufficient resin to bind the fillers tightly. The hybrid filler system has better properties than the single filler system. The experimental results indicate that there is an optimum composition range with respect to electrical conductivity and mechanical properties. [Copyright &y& Elsevier]

Curcumin (CUR) has been used in the treatment of various diseases such as cough, fever, skin disease, and infection because of various biological benefits such as anti-inflammatory, antiviral, antibacterial, and antitumor activity. However, CUR is a BCS class 4 group and has a limitation of low bioavailability due to low solubility and permeability. Therefore, the purpose of this study is to prepare a nanosuspension (NSP) loaded with CUR (CUR-NSP) using a statistical design approach to improve the oral bioavailability of CUR, and then to develop CUR-NSP coated with tannic acid to increase the mucoadhesion in the GI tract. Firstly, the optimized CUR-NSP, composed of sodium dodecyl sulfate (SDS) and polyvinylpyrrolidone/vinyl acetate (PVP/VA), was modified with tannic acid (TA). The particle size and polydispersity index of the formulation measured by laser scattering analyzer were 127.7 ± 1.3 nm and 0.227 ± 0.010, respectively. In addition, the precipitation in distilled water (DW) was 1.52 ± 0.58%. Using a differential scanning calorimeter and X-ray diffraction analysis, the stable amorphous form of CUR was confirmed in the formulation, and it was confirmed that CUR-NSP formulation was coated with TA through a Fourier transform-infrared spectroscopy. In the mucoadhesion assay using the turbidity, it was confirmed that TA-CUR-NSP had higher affinity for mucus than CUR-NSP under all pH conditions. This means that the absorption of CUR can be improved by increasing the retention time in the GI tract of the formulation. In addition, the drug release profile showed more than 80% release, and in the cellular uptake study, the absorption of the formulation (TA-CUR-NSP) containing TA acting as an inhibitor of P-gp was increased by 1.6-fold. In the evaluation of antioxidant activity, the SOD activity of TA-CUR-NSP was remarkably high due to TA, which improves cellular uptake and has antioxidant activity. In the pharmacokinetic evaluation, the maximum drug plasma concentration of the TA-coated NSP formulation was 7.2-fold higher than that of the pure drug. In all experiments, it was confirmed that the TA-CUR-NSP is a promising approach to overcome the low oral bioavailability of CUR. [ABSTRACT FROM AUTHOR]

The synthesis process or composition of mesoporous silica nanoparticles (MSNs) affects the physicochemical properties. Using these properties, MSNs were synthesized through the Box–Behnken design (BBD) among statistical experimental methods. The effect of the amounts of synthetic reagents, hexadecyl triethyl ammonium bromide (CTAB), tetraethyl orthosilicate (TEOS), and 2 N sodium hydroxide (NaOH), was studied using the reaction surface design. Surface area, particle size, and zeta potential were set as response values. The physicochemical properties of the optimized MSNs were evaluated, and the effect as a drug delivery system was evaluated by loading doxorubicin hydrochloride (DOX). Nano-sized MSNs were successfully prepared with 0.617 g of CTAB, 8.417 mL of TEOS, and 2.726 mL of 2 N NaOH and showed excellent physicochemical properties. The optimized MSNs showed negligible toxicity in MCF-7 cells. The drug release profile from DOX-loaded MSNs (MSN@DOX) showed an increased rate of release with decreasing pH of the medium, with the release profile sustained for 48 h. In the cytotoxicity test, the sustained drug release mechanism of MSN@DOX was confirmed. This study proposed a new statistical approach to the synthesis of MSNs. [ABSTRACT FROM AUTHOR]

• Fabrication of efficient bimetallic catalysts for OER. • Nickel decoration was performed on bimetallic CNT/CoNi. • Ni/CNT/CoNi exhibited excellent electrochemical performance and cycling stability. The fabrication of efficient catalysts for the oxygen evolution reactions (OER) that are required to accelerate the sluggish kinetics of metal-air batteries has attracted significant attention for application in energy conversion devices. Metal-organic frameworks (MOFs) have been recognized as potential candidates for the formation of promising catalysts. In this study, we report the formation of Ni/CNT/CoNi using bimetallic-ZIF (CoNi-ZIF) as a precursor. Bimetallic CoNi encapsulated in carbon nanotubes (CNTs) was obtained by calcinating CoNi-ZIF-67 to yield CNT/CoNi. The resulting CNT/CoNi was highly porous with a significant specific surface area of 242 m2/g. After calcination, Ni deposition on the CNT was performed and the surface area was reduced to 168.7 m2/g. Ni/CNT/CoNi was applied as a cathode material in zinc-air batteries, exhibiting excellent electrochemical performance and cycling stability. [ABSTRACT FROM AUTHOR]

• Metformin loaded HCFT was showed the sustained release profile. • Metformin loaded HCFT was successfully floated in the rabbit stomach over 6 h. • HCFT improved the oral bioavailability of metformin (around 123%, vs Glucophage® XR). Metformin has several problems such as low bioavailability, short half-life, and narrow absorption window, sustained and site-specific drug delivery system is required. Floating drug delivery systems are very useful to achieve these purposes. However, conventional floating systems have several limitations; lag time, a high proportion of excipient in the tablet, using non-biocompatible excipient, and requirement of a complicated procedure. To overcome these obstacles, we developed a hollow-core floating tablet (HCFT). The HCFT immediately floated in pH 1.2, 4.0, 6.8 medium, and even distilled water. The floating duration time of HCFT was>24 h. From the in vitro release study, it was confirmed that HCFT showed the sustain release profile of metformin for 12 h. Water uptake and matrix erosion were evaluated for predicting the buoyancy and drug release kinetics of HCFT in the body. Factor analysis was applied to optimize the formulation. There were significant (p < 0.05) differences in metformin plasma concentration of 4 h and 6 h between two groups. Compared with Glucophage® XR, the relative bioavailability of metformin HCFT was 123.81 ± 3.52%. The X-ray imaging of optimized formulation revealed that HCFT was constantly floating in the stomach region of the rabbit, thereby indicating improved gastric retention for>6 h. Consequently, all the findings indicate that HCFT could be an effective gastric retention system and applied extensively to other drugs with narrow absorption windows. [ABSTRACT FROM AUTHOR]

Nanostructured lipid carriers (NLC) are capable of encapsulating hydrophilic and lipophilic drugs. The present study developed an NLC containing epidermal growth factor (EGF) and curcumin (EGF–Cur-NLC). EGF–Cur-NLC was prepared by a modified water-in-oil-in-water (w/o/w) double-emulsion method. The EGF–Cur-NLC particles showed an average diameter of 331.8 nm and a high encapsulation efficiency (81.1% and 99.4% for EGF and curcumin, respectively). In vitro cell studies were performed using two cell types, NIH 3T3 fibroblasts and HaCaT keratinocytes. The results showed no loss of bioactivity of EGF in the NLC formulation. In addition, EGF–Cur-NLC improved in vitro cell migration, which mimics the wound healing process. Finally, EGF–Cur-NLC was evaluated in a chronic wound model in diabetic rats. We found that EGF–Cur-NLC accelerated wound closure and increased the activity of antioxidant enzymes. Overall, these results reveal the potential of the NLC formulation containing EGF and curcumin to promote healing of chronic wounds. [ABSTRACT FROM AUTHOR]

Obesity is a major health concern worldwide, and it is leading to worsening disease morbidity and mortality. Herbal supplements and diet-based therapies have attracted interest in the treatment of obesity. It is known that Garcinia cambogia (GA) and mulberry leaf, which contain polyphenols, have anti-obesity activity. Herein, we developed a combined tablet consisting of GA extract and bioconverted mulberry leaf extract (BMUL) using a statistical design approach. The ratio and amount of sustained polymers were set as factors. In the cell study, the combination of GA and BMUL showed synergistic anti-obesity activity. In a statistical model, the optimized amounts of hydroxypropyl methylcellulose 2208 (HPMC 2208) and polyethylene oxide 303 (POLYOX 303) were 41.02% and 58.98%, respectively. Additionally, the selected ratio of microcrystalline cellulose (MCC) was 0.33. When the release, hardness, and friability of the GABMUL tablet were evaluated, the error percentages of the response were lower than 10%. This indicates that the GABMUL tablet was successfully prepared. [ABSTRACT FROM AUTHOR]

We designed and synthesized a series of sulfonated poly(arylene ether sulfone) (SPES) with different hydrophilic or hydrophobic oligomer ratios using poly-condensation strategy. Afterward, we fabricated the corresponding membranes via a solution-casting approach. We verified the SPES membrane chemical structure using nuclear magnetic resonance (1H NMR) and confirmed the resulting oligomer ratio. Field-emission scanning electron microscope (FE-SEM) and atomic force microscope (AFM) results revealed that we effectively attained phase separation of the SPES membrane along with an increased hydrophilic oligomer ratio. Thermal stability, glass transition temperature (Tg) and membrane elongation increased with the ratio of hydrophilic oligomers. SPES membranes with higher hydrophilic oligomer ratios exhibited superior water uptake, ion-exchange capacity, contact angle and water sorption, while retaining reasonable swelling degree. The proton conductivity results showed that SPES containing higher amounts of hydrophilic oligomers provided a 74.7 mS cm−1 proton conductivity at 90 °C, which is better than other SPES membranes, but slightly lower than that of Nafion-117 membrane. When integrating SPES membranes with proton-exchange membrane fuel cells (PEMFCs) at 60 °C and 80% relative humidity (RH), the PEMFC power density exhibited a similar increment-pattern like proton conductivity pattern. [ABSTRACT FROM AUTHOR]

A simple, sensitive, and rapid UHPLC-MS/MS method was developed for the simultaneous determination of veratraldehyde and its metabolite veratric acid in rat plasma. Cinnamaldehyde was used as an internal standard (IS) and the one-step protein precipitation method with 0.2% formic acid in acetonitrile (mobile phase B) was used for the sample extraction. Reversed C18 column (YMC-Triart C18 column, 50 mm × 2.0 mm, 1.9 µm) was used for chromatographic separation and was maintained at 30 °C. The total run time was 4.5 min and the electrospray ionization in positive mode was used with the transition m/z 167.07 → 139.00 for veratraldehyde, m/z 183.07 → 139.00 for veratric acid, and m/z 133.00 → 55.00 for IS. The developed method exhibited good linearity (r2  ≥  0.9977), and the lower limits of quantification ranged from 3 to 10 ng/mL for the two analytes. Intra-day precision and accuracy parameters met the criteria (within ±15%) during the validation. The bioanalytical method was applied for the determination of veratraldehyde and veratric acid in rat plasma after oral and percutaneous administration of 300 and 600 mg/kg veratraldehyde. Using the analytical methods established in this study, we can confirm the absorption and metabolism of veratraldehyde in rats for various routes. [ABSTRACT FROM AUTHOR]

A surge of interest in microneedle (MN) vaccines as a novel vaccination system has emerged. Before the clinical application of MN vaccine, an assessment of potential biological risks to skin and quality control of MN must be performed. Therefore, the present study aims to evaluate the physicochemical properties of MN and to evaluate the histological changes and inflammatory cell infiltrations after the application of MN with hepatitis B surface antigen (HBsAg). During in vitro and in vivo release testing, HBsAg MN released over 70% of HBsAg at 30 min. During the pyrogen test of HBsAg MN in rabbit, no rabbit showed an individual rise in temperature of 0.5 °C or more. MN with HBsAg produced the moderate immunization in mice. MN application did not alter the thickness of dermal and epidermal layers in mice. In addition, the topical applications of MN and MN for hepatitis B vaccine did not acutely induce the inflammation, allergic reaction, dermal toxicity and skin irritation. Thus, the MN system for the delivery of HBsAg could be the promising technology in the hepatitis B vaccination. [ABSTRACT FROM AUTHOR]

In this study, we developed ticagrelor-dispersed nanosuspension (TCG-NSP) to enhance the dissolution and oral bioavailability of ticagrelor (TCG) through a statistical design approach. TCG, a reversible P2Y 12 receptor antagonist, is classified as a biopharmaceutics classification system (BCS) class IV drug with low solubility and permeability, resulting in low oral bioavailability. Nanosuspension (NSP) is an efficient pharmaceutical technique for overcoming the disadvantages. First, we optimized TCG-NSP consisting of D-α-Tocopherol polyethylene glycol 1000 succinate (TPGS) and polyvinyl alcohol (PVA), which exhibited homogeneously dispersed TCG particle (233 nm) and low precipitation (3%). Characterization studies demonstrated that TCG-NSP provided amorphous TCG particles and supersaturation effect, resulting in higher dissolution than a commercial product. In addition, everted gut sac and pharmacokinetic studies confirmed that TCG-NSP improved the gastrointestinal permeation of TCG by 2.8-fold compared to commercial product, thereby enhancing the oral bioavailability (2.2-fold). These results suggested that TCG-NSP could be successfully used as an efficient pharmaceutical formulation to achieve the enhanced dissolution and oral bioavailability of TCG. [ABSTRACT FROM AUTHOR]

Amine functionalized carbon nanotube (ANCT) is applied as an inorganic potential proton conducting material embedded in a sulfonated poly(ether ether ketone) (SPEEK) matrix. The morphological, structural, thermomechanical, physiochemical and electrochemical properties of SPEEK/ACNT composite were investigated and compared to obtained results from bare SPEEK. The synthesized ACNT-incorporated SPEEK membrane have uniform and dense morphology and exhibit improved properties as proton exchange membrane (PEM); for example, SPEEK/ACNT possessed higher thermal stability and tensile strength than SPEEK alone. The amine functionalized structure of ACNT is assumed to be one of critical factors resulting in higher performance of SPEEK/ACNT membrane, since it can induce acid-base conducting networks between ACNT and SPEEK matrix, which would improve water uptake and proton conductivity while lowering ion exchange capacity of membrane. When used in 20% relative humidity, a polymer electrolyte fuel cell (PEFC) with SPEEK/ACNT membrane is found to exhibit much higher performance than a PEFC with bare SPEEK, suggesting the potential use of SPEEK/ACNT membrane as PEM. Proton hopping mechanism between acid-base networks in SPEEK/ACNT composite. Image 1 • ACNT was employed as inorganic potential filler to prepare SPEEK/ACNT composite. • Addition of ACNT to SPEEK resulted in improved physiochemical and thermomechanical properties. • Optimized SPEEK/ACNT (1.5 wt%) exhibited improved PEFC performance under 20% RH while holding excellent durability compared to bare SPEEK. [ABSTRACT FROM AUTHOR]

• Synthesis and characterization of Co 3 O 4 -NFs by the calcination of Co(OH) 2 @SiO 2. • Fabrication of Ni@Co 3 O 4 -NFs by chemical deposition of nickel nanoparticles. • Higher catalytic activity for the OER and ORR. • Higher stability and longer life cycles. Co 3 O 4 nanoflowers (NFs) were obtained from cobalt hydroxide coated on silica, Co(OH) 2 @SiO 2 , prepared from a homogenous mixture of urea and cobalt nitrate in an aqueous solution. The Co 3 O 4 @SiO 2 was obtained by calcining Co(OH) 2 @SiO 2 under atmospheric air for 3 h and then immersing in sodium hydroxide to yield Co 3 O 4 -NFs. The Ni-deposited Co 3 O 4 NFs (Ni@Co 3 O 4 -NFs) were synthesized by chemical deposition of nickel nanoparticles onto Co 3 O 4 -NF by a reducing agent, NaBH 4. The physical characterization of Co 3 O 4 -NFs and Ni@Co 3 O 4 -NFs was performed by Brunauer-Emmett-Teller analysis, scanning electron microscopy and X-ray diffraction. The electrochemical properties of Co 3 O 4 -NFs and Ni@Co 3 O 4 -NFs for the oxygen reduction and evolution reaction were determined in an 8 M KOH solution. Ni@Co 3 O 4 -NF showed a better cell performance than that of Co 3 O 4 -NF. Moreover, Ni@Co 3 O 4 -NF exhibited a higher stability and longer life cycles at 20 mA cm−2 at a 2 h charging and discharging rate as compared to Co 3 O 4 -NF. Therefore, Co 3 O 4 -NF and Ni@Co 3 O 4 -NF could be used as a cathode material for Zn-air rechargeable batteries. [ABSTRACT FROM AUTHOR]

Recently, Achyranthis radix extract has been studied as a therapeutic agent for dry eye disease that occurs from fine dust. The aim of this study was the development of Achyranthis radix extract-loaded eye drop formulations using lubricants, generally used for artificial tear eye drops. Ecdysterone was used as a marker compound for Achyranthis radix extract and 1% Achyranthis radix extract solution contained 14.37 ± 0.04 μg/mL of ecdysterone. Before formulation studies, a new method was performed to evaluate pigmentation, which might be caused by eye drops of herbal extract. A comparative study of the water retention ability of each formulation and ability to prevent the death of conjunctival epithelial cells in dry conditions was conducted. Moreover, treatment of Achyranthis radix extract (USL) eye drop formulation exhibited a significant inhibitory effect on inflammation in a concentration-dependent manner. The long-term and accelerated stability tests showed that lubricants could contribute to the stability of herbal extracts in solution. In conclusion, hyaluronic acid showed a good effect on the development of eye drop formulation using Achyranthis radix extracts for treating dry eye disease. [ABSTRACT FROM AUTHOR]

Diabetes mellitus (DM) has become a major health problem in most countries of the world. DM causes many complications, including hyperglycemia, diabetic ketoacidosis, and death. In Asia, mulberry has been used widely in the treatment of DM. Combination of drugs with herbal medicine may reduce the unwanted side effects caused by drugs. In this study, the influence of extended mulberry leaves extract (MLE) intake on metformin (Met) was evaluated in terms of pharmacokinetics and pharmacodynamics in DM-induced rats. Three week-treatment of MLE alone produced the anti-hyperglycemic effect (around 24%) if compared to the control. Interestingly, Met administration after MLE treatment for 3 weeks enhanced about 49% of the anti-hyperglycemic effect of Met. In addition, the extended intake of MLE potentiated the anti-hyperglycemic effect of Met on various concentrations. This potentiated anti-hyperglycemic effect of Met appears to be due to the pharmacokinetic change of Met. In this study, 3 week-treatment of MLE reduced the elimination of Met in DM-induced rats. In addition, MLE reduced the human organic cation transporter 2 (hOCT2) activity in a concentration-dependent manner. Thus, these findings suggest that MLE lowered the elimination of Met via inhibiting the hOCT2. [ABSTRACT FROM AUTHOR]

The aim of this study was to solidify a ticagrelor loaded self-microemulsifying drug delivery system (TCG-SM) with enhanced dissolution and bioavailability of ticagrelor (TCG) for developing TCG-SM granules and tablets. TCG was dissolved in the self-microemulsifying drug delivery system (SMEDDS) and TCG-SM was solidified by adsorption to the optimized adsorbent through statistical design. In order to select an appropriate adsorbent, the physical properties (bulk density, tapped density, angle of repose, and liquid adsorption capacity) of silica-based adsorbents (Neusilin US2, Florite R, Aerosil 200, and Florite PS-10) and non silica-based adsorbents (Avicel PH102, Pharmatose 100M, Pearlitol 200, LH-11, and Emcompress) were investigated. Neusilin US2 and Florite R were selected as suitable adsorbents and their mixing ratios were optimized using statistical experimental design. The predicted values of physical properties by statistical design showed the error percentage of <10% compared to actual values. As a result of the statistical approach, TCG-SM (490 mg) was successfully solidified with Nesulin US2 (167.8 mg) and Florite R (82.2 mg), which showed good powder properties and improved dissolution of TCG. The solidified TCG-SM (Sol-TCG-SM), disintegrant (croscarmellose sodium), diluent (microcrystalline cellulose), binder (polyvinylpyrrolidone), and lubricant (magnesium stearate) were mixed to prepare granules. And, the granules with total weight of 900 mg were tableted using 16 mm oval-shape punch. The prepared Sol-TCG-SM tablet showed good tablet properties and maintained self-microemulsifying ability, such as microemulsion formation and enhanced dissolution of TCG. In vivo pharmacokinetic study, the relative bioavailability of Sol-TCG-SM exhibited 108.1% and 632.7% compared to TCG-SM and raw TCG powder, respectively. In conclusion, we successfully solidified SMEDDS with improved oral bioavailability of insoluble drugs such as TCG through a statistical design. This suggests a new approach that can be utilized in the production of solidified SMEDDS. Unlabelled Image • TCG-SM with enhanced dissolution and oral bioavailability was solidified via statistical approach. • The Sol-TCG-SM exhibited the acceptable powder properties and the improved dissolution than raw ticagrelor. • The granulation and tableting of Sol-TCG-SM was successfully carried out through screening study of disintegrants. • The bioavailability of Sol-TCG-SM was similar to that of TCG-SM, which is superior to raw ticagrelor. [ABSTRACT FROM AUTHOR]

Tadalafil is a cytochrome P450 (CYP) 3A4 substrate. Because there are few data on drug-drug interactions, it is advisable to take sufficient consideration when co-administering tadalafil with CYP3A4 inducers or inhibitors. This study was conducted to assess the effect of ticagrelor, a CYP3A4 inhibitor, on the pharmacokinetic properties of tadalafil after oral administration to rats. A total of 20 Sprague–Dawley male rats were randomly divided into the non-pretreated group and ticagrelor-pretreated group, and tadalafil was orally administered to each group after pretreatment with or without ticagrelor. Blood samples were collected at predetermined time points after oral administration of tadalafil. As a result, systemic exposure of tadalafil in the ticagrelor-pretreated group was significantly increased compared to the non-pretreated group (1.61-fold), and the clearance of tadalafil in the ticagrelor-pretreated group was significantly reduced than the non-pretreated group (37%). The prediction of the drug profile through the one-compartment model could explain the differences of pharmacokinetic properties of tadalafil in the non-pretreated and ticagrelor-pretreated groups. This study suggests that ticagrelor reduces a CYP3A-mediated tadalafil metabolism and that tadalafil and a combination regimen with tadalafil and ticagrelor requires dose control and specific pharmacotherapy. [ABSTRACT FROM AUTHOR]

Strategies for the development of anticancer drug delivery systems have undergone a dramatic transformation in the last few decades. Lipid-based drug delivery systems, such as a nanostructured lipid carrier (NLC), are one of the systems emerging to improve the outcomes of tumor treatments. However, NLC can act as an intruder and cause an immune response. To overcome this limitation, biomimicry technology was introduced to decorate the surface of the nanoparticles with various cell membrane proteins. Here, we designed paclitaxel (PT)-loaded nanostructured lipid carrier (PT-NLC) with platelet (PLT) membrane protein because PLT is involved with angiogenesis and interaction of circulating tumor cells. After PLT was isolated from blood using the gravity-gradient method and it was used for coating PT-NLC. Spherical PT-NLC and platelet membrane coated PT-NLC (P-PT-NLC) were successfully fabricated with high encapsulation efficiency (EE) (99.98%) and small particle size (less than 200 nm). The successful coating of PT-NLC with a PLT membrane was confirmed by the identification of CD41 based on transmission electron microscopy (TEM), western blot assay and enzyme-linked immunosorbent assay (ELISA) data. Moreover, the stronger affinity of P-PT-NLC than that of PT-NLC toward tumor cells was observed. In vitro cell study, the PLT coated nanoparticles successfully displayed the anti-tumor effect to SK-OV-3 cells. In summary, the biomimicry carrier system P-PT-NLC has an affinity and targeting ability for tumor cells. [ABSTRACT FROM AUTHOR]

Ticagrelor (TGL), a P2Y12 receptor antagonist, is classified as biopharmaceutics classification system (BCS) class IV drug due to its poor solubility and permeability, resulting in low oral bioavailability. Nanostructured lipid carriers (NLC) are an efficient delivery system for the improvement of bioavailability of BCS class IV drugs. Hence, we prepared TGL-loaded NLC (TGL-NLC) to enhance the oral bioavailability and antiplatelet activity of TGL with a systemic design approach. The optimized TGL-NLC with Box–Behnken design showed a small particle size of 87.6 nm and high encapsulation efficiency of 92.1%. Scanning electron microscope (SEM), differential scanning calorimetry (DSC), and powder X-ray diffraction (PXRD) were performed to investigate the characteristics of TGL-NLC. Furthermore, TGL-NLC exhibited biocompatible cytotoxicity against Caco-2 cells. Cellular uptake of TGL-NLC was 1.56-fold higher than that of raw TGL on Caco-2 cells. In pharmacokinetic study, the oral bioavailability of TGL-NLC was 254.99% higher than that of raw TGL. In addition, pharmacodynamic study demonstrated that the antiplatelet activity of TGL-NLC was superior to that of raw TGL, based on enhanced bioavailability of TGL-NLC. These results suggest that TGL-NLC can be applied for efficient oral absorption and antiplatelet activity of TGL. [ABSTRACT FROM AUTHOR]