Latest ArticlesThe aim of this study is to prepare acetaminophen sustained-release tablets by hot melt extrusion 3D printing technology based on the concept of "Quality by Design" (QbD). Firstly, the failure mode and effect analysis (FMEA) was used to determine the critical process parameters (CPPs), then full-factor experimental design was used to analyze the critical quality attributes (CQAs) and to establish the design space. The results showed that the content of plasticizer, the path spacing and the shell numbers are independent variable for the experimental design. The design space was concluded to be plasticizer content:9%, and the shell number:3-5, the path spacing:1.05-1.2 mm. In this study, 3D printing technology was used to prepare acetaminophen sustained-release tablets in accordance with the concept of QbD, which improved the durability of the process and ensured the uniform and controllable quality of the preparation and also provided experimental basis for personalised medicine.
It is now widely accepted that platelet aggregation plays an important role in physiological hemostasis and pathological thrombosis associated with cardiovascular and cerebrovascular diseases. Anti-platelet aggregation drug research is also a hot spot of current research. The biggest challenge of antiplatelet therapy has been the molecular overlap of the hemostasis and thrombosis, leading to a serious risk of bleeding. Recent studies have emphasized the importance of shear stress generated from blood flow, which will primarily drive platelet activation and aggregation in thrombosis. So if we can take advantage of the differences between the physiological and pathological vascular blood flow environment, the development of selective anti-platelet therapy may be a safer treatment for cardiovascular and cerebrovascular diseases. In this review, we discuss the underlying mechanisms of shear-induced platelet activation. Later, we summarize the effects and mechanisms of compounds and traditional Chinese medicine on shear-induced platelet activation. The aim is to provide a reference for the study of biological pharmacology of traditional Chinese medicine for promoting blood circulation and removing blood stasis.
Epithelial cell adhesion molecule (EpCAM) is a popular target for cancer therapy. In this research, 3 nanobodies with high specificity and endocytosis activity against EpCAM were developed, which provides a basis for the study of immunotoxin based on EpCAM. In our preliminary experiments, we have immunized a camel with EpCAM-Fc antigen and constructed a high-quality phage display library. Seventeen nanobodies with different complementarity determining region (CDR) 3 sequences have been screened after 3 rounds of biopanning by phage display technology. The animal procedures were approved by the Institutional Animal Care and Use Committee (IACUC) of Fudan University School of Pharmacy. After purification, 7 nanobodies showed high cell binding activity by fluorescent activated cell sorting (FACS) identification. Furthermore, 3 nanobodies presented high endocytosis activity based on FACS and laser confocal microscopy, which also showed high affinity to EpCAM measured by ForteBio. According to this study, we aimed to provide a novel alternative approach to the EpCAM-targeted therapy and to provide guidance for the study of nanobody based immunotoxins for other targets.
Drug-drug complexes play important roles in improving the physicochemical properties of drugs including the solubility, dissolution rate and stability of the active pharmaceutical ingredients (APIs). In this paper, the design, synthesis, characterization, changes in physicochemical and pharmacologic properties, structural polymorphisms and the research and development pipelines of a variety of drug-drug cocrystals/salts synthesized based on the crystal engineering design are reviewed. This may provide theoretical support for the development of the new solid-state combinational drugs.
Tumor immune therapy has been remarkably successful in recent years and several kinds of PD-1/PD-L1 (programmed death-1/programmed death-ligand 1) antibody drugs have been approved by the FDA for treatment of advanced malignant neoplasms. However, as biomacromolecules these antibody drugs have certain drawbacks such as high cost, injection-only administration and immunogenicity; thus, we turned to small molecules that have lower immune risks and better modifiability. Considering the structural diversity of natural products, we chose to investigate the active components in Panax ginseng, a famous and highly valued traditional Chinese medicine. Nine compounds were separated and identified in this research using a HPLC-coupled MS system, and 3 PD-1 binding compounds were identified using the SPR method. The PD-1/PD-L1 inhibitory ability of ginsenoside Rg1, as a representative ginsenoside, was verified by cytopharmacological methods. This research provides a new method for the identification of immune blockade inhibitors in natural products.
K-values of 56 batches of 7 types of povidone were measured by microfluidic rheometry and with a Ubbelohde capillary viscometer. The K-values of the two methods were tested by SPSS software and the results showed that there was no significant difference between the two methods (P > 0.05). Taking K-values measured with the Ubbelohde capillary viscometer (Ku) as the abscissa and K-values measured by microfluidic rheometry (Km) as the ordinate a linear equation was calculated:Km=0.893 9Ku + 4.617 6, R2=0.986 2, with good linearity, indicating that the microfluidic rheometer method can replace the Ubbelohde capillary viscometer in determining K-values of povidone. The microfluidic rheometer method has the benefits of less sample consumption, faster determination, and is more accurate, and it can be used with high-throughput automatic acquisition, which provides a more convenient method for the determination of K-values of different types of povidone. The weight-average molecular weights (Mw) of each type of povidone were measured by gel permeation chromatography-multi angle laser light scattering (GPC-MALLS), and the relationship between Mw and Km was lgMw=-0.000 4 Km2 + 0.072 7 Km + 2.791, R2 =0.990 1. The fitting relationship was good, and Mw could be calculated by Km by the equation.
We investigated the ability of 3-bromopyruvic acid to increase the sensitivity of tamoxifen-resistant MCF-7/TR cells to tamoxifen and to explore the underlying mechanism. 4-Hydroxy tamoxifen (4-OHT) is the active form of tamoxifen in vivo and was used in this study. The effect of 3-bromopyruvic acid on the viability of MCF-7/TR cells was measured by MTT assay and the morphology of MCF-7/TR cells was observed with an inverted microscope. The results show that 3-bromopyruvic acid at 40 μmol·L-1 has no significant effect on the viability of MCF-7/TR cells, and this concentration was used in the subsequent experiments:3-bromopyruvic acid significantly increased the inhibitory effect of 4-OHT on the viability of MCF-7/TR cells, with a reversal-fold of 1.91, as determined by MTT assay; the lactate level, determined with a lactate detection kit, and the expression levels of GLUT1, HK2, and LDHA in MCF-7/TR cells as measured by immunoblotting were significantly higher than in MCF-7 cells; and compared with 4-OHT treatment alone, the combination treatment of 3-bromopyruvic acid and 4-OHT significantly reduced the lactate level and the expression of GLUT1, HK2, LDHA in MCF-7/TR cells. The above results show that 3-bromopyruvic acid increases the sensitivity of MCF-7/TR cells to tamoxifen, and the mechanism is related to the inhibition of aerobic glycolysis.
In recent years, the number of clinical trials of stem cell products has increased, and the research and development technology and evaluation system have developed rapidly. Human pluripotent stem cell (hPSC)-derived cellular products are in the phase Ⅰ/Ⅱ stage of clinical trials. Related products include hPSC-derived neurons, retinal pigment epithelial cells, pancreatic beta cells, etc. They are generally used for the repair and replacement of functional cells related to degenerative diseases and genetic diseases via local transplantation. So far, no similar products have been officially approved on market. As hPSC possesses multi-directional differentiation potential and the ability to form teratoma in vivo, compared with other stem cell products, hPSC-derived cellular products have relatively higher risk of tumorigenicity, longer differentiation induction cycle, more complex production process, together with the rapidly updating quality characterization methods, which pose challenges to the scientific evaluation of their human applications. Based on the problems in the recent review and communication of clinical trial applications of stem cell products, and with reference to the relevant technical guidelines, this paper proposes the chemistry, manufacturing, and controls review considerations on the manufacturing process and quality study of hPSC-derived cellular products. We hope to improve the communications between developers and regulators.
The intestinal flora is a diverse microbial community living in the digestive tract of humans and animals. This microbial community can modify drugs in unpredictable ways, leading to changes in the pharmacokinetics of drugs in vivo and affecting their clinical efficacy. Here we review drug metabolism mediated by intestinal flora from three aspects:prodrug activation, drug inactivation, and toxicity. The effect of the stable hypoxic environment on the composition and quantity of intestinal flora and the effect on drug metabolism are discussed. Understanding the influence of intestinal flora on drug metabolism is not only conducive to individualized medication, but also conducive to rational drug design, allowing us to predict and understand individual drug response and regulate the intestinal microbiome to improve drug efficacy, thus promoting personalized medicine.
In recent years, with rapid advances in chlorogenic acid (CGA) research, it has become widely used in medicine, the chemical industry and health care products, with the potential for broad application. CGA is a water-soluble phenolic natural product and is extensively distributed in a variety of plants. Numerous studies have shown that CGA has strong biological activities including antibacterial, antiviral, antitumor, antioxidative, anti-inflammatory and metabolic regulatory activities. This review summarizes the pharmacological effects as well as the underlying mechanisms of CGA, providing an important theoretical basis for further research on CGA drug targets and potential mechanisms.
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