The purpose of this study was to investigate the efficacy of hydrophilic polymers in a solid dispersion formulation in improving the solubility and dissolution rate of rivaroxaban (RXB), a poorly ...soluble drug. The developed solid dispersion consisted of two components, a drug and a polymer, and the drug was dispersed as amorphous particles in a polymer matrix using the spray drying method. Polymeric solid dispersions were evaluated using solubility tests, in vitro dissolution tests, powder X-ray diffraction, differential scanning calorimetry, scanning electron microscopy, and particle size distribution analysis. To maximize physical stability against crystallization and improve the solubility and dissolution of RXB, it is important to select the appropriate polymer type and the optimal ratio of the polymer to the drug. The optimized polyvinyl alcohol (PVA)-based (1/0.5, w/w) and gelatin-based (1/5, w/w) solid dispersion formulations showed 6.3 and 3.6 times higher drug solubilities than pure RXB powder, respectively, and the final dissolution rate was improved by approximately 1.5 times. Scanning electron microscopy and particle size distribution analyses confirmed that the gelatin-based solid dispersion was smaller and more spherical than the PVA-based solid dispersion, suggesting that the gelatin-based solid dispersion had a faster initial dissolution rate. Differential scanning calorimetry and powder X-ray diffraction analyses confirmed that RXB had successfully changed from a crystalline form to an amorphous form, contributing to the improvement in its solubility and dissolution rate. This study provides a strategy for selecting suitable polymers for the development of amorphous polymer solid dispersions that can overcome precipitation during dissolution and stabilization of the amorphous state. In addition, the selected polymer solid dispersion improved the drug solubility and dissolution rate of RXB, a poorly soluble drug, and may be used as a promising drug delivery system.
The National Culture Collection of Pathogens (NCCP) is a microbial resource bank in Korea that collects pathogen resources causing infectious disease in human and distributes them for research and ...education. The NCCP bank attempts to discover strains with various characteristics and specific purposes to provide diverse resources to researchers.
Staphylococcus aureus
American Type Culture Collection (ATCC) 6538P is used as a reference strain in the microbial assay for antibiotics in the Korean and in the United States Pharmacopoeias. We aimed to analyze domestically isolated microbial resources from the NCCP to replace the
S. aureus
reference strain.
Staphylococcus aureus
strains were identified using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and the VITEK-2 system and characterized by multilocus sequence typing, 16S rRNA sequencing, and antibiotic susceptibility testing. Several candidate strains had similar characteristics as the reference strain. Among them, the nucleotide sequence of the 16S rRNA region of NCCP 16830 was 100% identical to that of the reference strain; it was sensitive to six types of antibiotics and showed results most similar to the reference strain. A validity evaluation was conducted using the cylinder-plate method. NCCP 16830 presented valid results and had the same performance as ATCC 6538P; therefore, it was selected as an alternative candidate strain.
The aim of this study was to evaluate whether stage at cancer diagnosis differed according to patient economic status.
A total of 10,528 patients with cancer of the stomach, colorectum, breast, or ...cervix, which are target organs of the Korean National Cancer Screening Program (NCSP; fully implemented in 2005) were extracted from population-based cancer registries. The patients were classified into four groups based on socioeconomic status (SES), as determined using their National Health Insurance (NHI) monthly premium at the time of cancer diagnosis. Cancer stage at diagnosis was defined as early (in situ/local) or late stage (regional/distant) based on the Surveillance, Epidemiology, and End Results (SEER) summary stage. Multivariable logistic regression analysis was performed to estimate the risk of non-local stage using age, residential area, and community deprivation index as covariates.
The lowest SES subjects showed significantly higher risks of being diagnosed at a later stage for stomach, colorectal, and female breast cancer, but not for cervical cancer, compared with the highest SES subjects. The estimated ORs were 1.28 (95% CI, 1.10–1.49), 1.29 (95% CI, 1.03–1.61), and 1.35 (95% CI, 1.02–1.81) in the lowest SES subjects with stomach, colorectal, and breast cancer, respectively.
In conclusion, later stage diagnoses of stomach, colon, and female breast cancer are still associated with SES in Korea in the era of the NCSP for the lower SES population.
•Advanced stage was more frequent in cancer patients with lower economic status.•Differences of stage by SES were found in stomach, colorectal, and breast cancer.•Disparities still exist after the National Cancer Screening program in Korea.
Endocrine therapy resistance in hormone receptor-positive/HER2-negative (HR+/HER2-) breast cancer (BC) is a significant clinical challenge that poses several unmet needs in the management of the ...disease. This study aimed to investigate the prognostic value of c-MET-positive circulating tumor cells (cMET+ CTCs), ESR1/PIK3CA mutations, and cell-free DNA (cfDNA) concentrations in patients with hormone receptor-positive (HR+) metastatic breast cancer (mBC).
Ninety-seven patients with HR+ mBC were prospectively enrolled during standard treatment at Samsung Medical Center. CTCs were isolated from blood using GenoCTC
and EpCAM or c-MET CTC isolation kits. PIK3CA and ESR1 hotspot mutations were analyzed using droplet digital PCR. CfDNA concentrations were calculated using internal control copies from the ESR1 mutation test. Immunocytochemistry was performed to compare c-MET overexpression between primary and metastatic sites.
The proportion of c-MET overexpression was significantly higher in metastatic sites than in primary sites (p = 0.00002). Survival analysis showed that c-MET+ CTC, cfDNA concentration, and ESR1 mutations were significantly associated with poor prognosis (p = 0.0026, 0.0021, and 0.0064, respectively) in HR+/HER2- mBC. By contrast, EpCAM-positive CTC (EpCAM+ CTC) and PIK3CA mutations were not associated with progression-free survival (PFS) in HR+/HER2- mBC. Multivariate analyses revealed that c-MET+ CTCs and cfDNA concentration were independent predictors of PFS in HR+/HER2- mBC.
Monitoring c-MET+ CTC, rather than assessing c-MET expression in the primary BC site, could provide valuable information for predicting disease progression, as c-MET expression can change during treatment. The c-MET+ CTC count and cfDNA concentration could provide complementary information on disease progression in HR+ /HER2- mBC, highlighting the importance of integrated liquid biopsy.
Remotely controlled, localized drug delivery is highly desirable for potentially minimizing the systemic toxicity induced by the administration of typically hydrophobic chemotherapy drugs by ...conventional means. Nanoparticle-based drug delivery systems provide a highly promising approach for localized drug delivery, and are an emerging field of interest in cancer treatment. Here, we demonstrate near-IR light-triggered release of two drug molecules from both DNA-based and protein-based hosts that have been conjugated to near-infrared-absorbing Au nanoshells (SiO₂ core, Au shell), each forming a light-responsive drug delivery complex. We show that, depending upon the drug molecule, the type of host molecule, and the laser illumination method (continuous wave or pulsed laser), in vitro light-triggered release can be achieved with both types of nanoparticle-based complexes. Two breast cancer drugs, docetaxel and HER2-targeted lapatinib, were delivered to MDA-MB-231 and SKBR3 (overexpressing HER2) breast cancer cells and compared with release in noncancerous RAW 264.7 macrophage cells. Continuous wave laser-induced release of docetaxel from a nanoshell-based DNA host complex showed increased cell death, which also coincided with nonspecific cell death from photothermal heating. Using a femtosecond pulsed laser, lapatinib release from a nanoshell-based human serum albumin protein host complex resulted in increased cancerous cell death while noncancerous control cells were unaffected. Both methods provide spatially and temporally localized drug-release strategies that can facilitate high local concentrations of chemotherapy drugs deliverable at a specific treatment site over a specific time window, with the potential for greatly minimized side effects.
We prove local and global well–posedness results for the Gabitov–Turitsyn or dispersion managed nonlinear Schrödinger equation with a large class of nonlinearities and arbitrary average dispersion on ...L2(R) and H1(R) for zero and non–zero average dispersions, respectively. Moreover, when the average dispersion is non–negative, we show that the set of ground states is orbitally stable. This covers the case of non–saturated and saturated nonlinear polarizations and yields, for saturated nonlinearities, the first proof of orbital stability.
Abstract
We consider the dispersion managed power-law nonlinear Schrödinger (DM NLS) equations with a small parameter
ɛ
> 0 and the averaged equation, which are used in optical fiber communications. ...We prove that the solutions of DM NLS equations converge to the solution of the averaged equation in
H
1
(
R
)
as
ɛ
goes to zero. Meanwhile, in the positive average dispersion, we obtain the global existence of the solution to DM NLS equation in
H
1
(
R
)
for sufficiently small
ɛ
> 0, even when the exponent of the nonlinearity is beyond the mass-critical power.
We investigated the physicochemical and rheological properties of black pudding prepared with duck blood using various combinations of cereal fiber sources: oat, buckwheat, quinoa, amaranth, and ...sorghum. The processing yield of black pudding made with duck blood and the cereals was higher than that of the control (without cereals) in all cases (P < 0.05). The moisture content of the black pudding was the highest in the buckwheat and amaranth groups (P < 0.05). The water activity, pH, and yellowness of the black pudding combined with duck blood and cereals were lower than that of the control (P < 0.05). The hardness of the black pudding with duck blood and cereals was higher than that of the control (P < 0.05), except for the amaranth group. The cohesiveness, gumminess, and chewiness of the black pudding with duck blood and cereals were higher than that of the control (P < 0.05). Differential scanning colorimetry showed distinct peak points according to treatment at the same temperature, and all treatments exhibited 2 peak temperatures, except for sorghum. The viscosities of all samples, including the control, decreased as the shear rate increased, and the viscosity of the black pudding with oat was slightly lower than that of the other samples. Thus, black pudding prepared with duck blood and cereal fibers showed excellent physicochemical and rheological properties, suggesting an improved processing method. These findings can further the development of products using duck blood as a valuable nutritional source rather than being lost as a by-product during slaughter.
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