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This study investigated the effect of different carrier materials on the in vitro properties of progesterone solid dispersions. The solid dispersions of the insoluble drug progesterone were prepared by hot melt extrusion technique using rheological properties as the index of investigation, and the in vitro properties of the solid dispersions were characterized. Scanning electron microscope revealed solid dispersions with rough surfaces and agglomerated microstructures into irregular lumpy particles. Differential scanning calorimetry and powder X-ray diffraction showed the change of progesterone crystalline form in solid dispersions from crystalline to amorphous state. In vitro dissolution studies showed that solid dispersions prepared with different carrier materials can effectively improve the dissolution rate of drugs. The results of the study showed that the type of carrier material had a significant effect on the in vitro properties of solid dispersions, providing a reference for the study of solid dispersions in the controlled release of insoluble drugs.
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@#Meningococcal polysaccharide conjugate vaccine is basically produced by chemical combination,and the most commonly used method is amide condensation reaction.Because of the covalent bonds between polysaccharide and protein,the prepared conjugate vaccine has high stability and good technical advantages,which plays an important role in the prevention of meningococcal related diseases.The vaccine can be applied to the immunization of young children under 2years old,and has more lasting protective effect.In this paper,the factors influencing the preparation of meningococcal polysaccharide conjugate vaccine,the binding mode of polysaccharide and carrier protein,the present situation at home and abroad and the existing problems in the preparation process were reviewed.
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Chinese materia medica has a wide range of clinical applications， but it has many active ingredients with different physicochemical properties， and the target organs， action pathways and mechanisms for different ingredients to exert their efficacy are not the same. Therefore， it is difficult to design and develop a co-delivery system loading multiple components of Chinese materia medica to maximize the synergistic therapeutic efficiency. Based on the characteristics of effectiveness and functionality of active ingredients， the strategies for multi-component co-delivery of Chinese materia medica can be categorized into two types：firstly， based on the effectiveness of active ingredients， new carriers such as liposomes， nanoparticles can be constructed to load multi-components of Chinese materia medica. secondly， based on the functionality of some active ingredients of Chinese materia medica， they are employed in the construction of co-delivery system， which can give play to the dual characteristics of their own efficacy and preparation functions. In this paper， we summarized the relevant research progress of the above two types of multi-component co-delivery strategies， and mainly discussed the pharmaceutical functions of the active ingredients in co-delivery systems， in order to find a more suitable multi-component co-delivery strategy， promoting the design and development of new delivery systems of Chinese materia medica.
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ABSTRACT Objective: To explore the effect of ischemic postconditioning on myocardial ischemia-reperfusion-induced acute lung injury (ALI). Methods: Forty adult male C57BL/6 mice were randomly divided into sham operation group (SO group), myocardial ischemia-reperfusion group (IR group), ischemic preconditioning group (IPRE group) and ischemic postconditioning group (IPOST group) (10 mice in each group). Anterior descending coronary artery was blocked for 60 min and then reperfused for 15 min to induce myocardial IR. For the IPRE group, 3 consecutive cycles of 5 min of occlusion and 5 minutes of reperfusion of the coronary arteries were performed before ischemia. For the IPOST group, 3 consecutive cycles of 5 min reperfusion and 5 minutes of occlusion of the coronary arteries were performed before reperfusion. Pathological changes of lung tissue, lung wet-to-dry (W/D) weight ratio, inflammatory factors, oxidative stress indicators, apoptosis of lung cells and endoplasmic reticulum stress (ERS) protein were used to evaluate lung injury. Results: After myocardial IR, lung injury worsened significantly, manifested by alveolar congestion, hemorrhage, structural destruction of alveolar septal thickening, and interstitial neutrophil infiltration. In addition, lung W/D ratio was increased, plasma inflammatory factors, including interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-17A, were increased, malondialdehyde (MDA) activity of lung tissue was increased, and superoxide dismutase (SOD) activity was decreased after myocardial IR. It was accompanied by the increased protein expression levels of ERS-related protein glucose regulatory protein 78 (GRP78), CCAAT/enhancer-binding protein (C/EBP) homologous protein (CHOP), and caspase-12, and the increased apoptotic indices of lung tissues. Conclusion: IPOST can effectively improve myocardial IR-induced ALI by inhibiting ERS-induced apoptosis of alveolar epithelial cells.
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As one of the traditional computer simulation techniques, molecular simulation can intuitively display and quantify molecular structure and explain experimental phenomena from the microscopic molecular level. When the simulation system increases, the amount of calculation will also increase, which will cause a great burden on the simulation system. Coarse-grained molecular dynamics is a method of mesoscopic molecular simulation, which can simplify the molecular structure and improve computational efficiency, as a result, coarse-grained molecular dynamics is often used when simulating macromolecular systems such as drug carrier materials. In this article, we reviewed the recent research results of using coarse-grained molecular dynamics to simulate drug carriers, in order to provide a reference for future pharmaceutical preparation research and accelerate the entry of drug research into the era of precision drug design.
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Molecular Dynamics Simulation , Drug CarriersABSTRACT
OBJECTIVE@#This study was aimed at investigating the carrier rate of, and molecular variation in, α- and β-globin gene mutations in Hunan Province.@*METHODS@#We recruited 25,946 individuals attending premarital screening from 42 districts and counties in all 14 cities of Hunan Province. Hematological screening was performed, and molecular parameters were assessed.@*RESULTS@#The overall carrier rate of thalassemia was 7.1%, including 4.83% for α-thalassemia, 2.15% for β-thalassemia, and 0.12% for both α- and β-thalassemia. The highest carrier rate of thalassemia was in Yongzhou (14.57%). The most abundant genotype of α-thalassemia and β-thalassemia was -α 3.7/αα (50.23%) and β IVS-II-654/β N (28.23%), respectively. Four α-globin mutations [CD108 (ACC>AAC), CAP +29 (G>C), Hb Agrinio and Hb Cervantes] and six β-globin mutations [CAP +8 (C>T), IVS-II-848 (C>T), -56 (G>C), beta nt-77 (G>C), codon 20/21 (-TGGA) and Hb Knossos] had not previously been identified in China. Furthermore, this study provides the first report of the carrier rates of abnormal hemoglobin variants and α-globin triplication in Hunan Province, which were 0.49% and 1.99%, respectively.@*CONCLUSION@#Our study demonstrates the high complexity and diversity of thalassemia gene mutations in the Hunan population. The results should facilitate genetic counselling and the prevention of severe thalassemia in this region.
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Humans , beta-Thalassemia/genetics , alpha-Thalassemia/genetics , Hemoglobinopathies/genetics , China/epidemiology , High-Throughput Nucleotide SequencingABSTRACT
@#Fibracel carriers based on polyester fiber have the advantages of good acid and alkali resistance,heat resistance,good biocompatibility,non-biodegradation,and can promote cell adhesion and growth. With no animal-derived ingredients and high biological safety,it is one of the preferred carriers for cell culture matrixes,which has been widely used in the development and production of cell matrix biological products with the development of biotechnology in recent years. This paper reviewed the structure and cell culture characteristics of fibracel carriers as well as the applications in vaccine production,cell therapy and tissue engineering,so as to provide a theoretical basis for the further development and application of fibracel carrier technology.
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Traditional microtubule inhibitors fail to significantly enhance the effect of colorectal cancer;hence,new and efficient strategies are necessary.In this study,a supramolecular nanoreactor(DOC@TA-Fe3+)based on tannic acid(TA),iron ion(Fe3+),and docetaxel(DOC)with microtubule inhibition,reactive oxygen species(ROS)generation,and glutathione peroxidase 4(GPX4)inhibition,is prepared for ferroptosis/apoptosis treatment.After internalization by CT26 cells,the DOC@TA-Fe3+nanoreactor escapes from the lysosomes to release payloads.The subsequent Fe3+/Fe2+conversion mediated by TA reducibility can trigger the Fenton reaction to enhance the ROS concentration.Additionally,Fe3+can consume gluta-thione to repress the activity of GPX4 to induce ferroptosis.Meanwhile,the released DOC controls microtubule dynamics to activate the apoptosis pathway.The superior in vivo antitumor efficacy of DOC@TA-Fe3+nanoreactor in terms of tumor growth inhibition and improved survival is verified in CT26 tumor-bearing mouse model.Therefore,the nanoreactor can act as an effective apoptosis and ferroptosis inducer for application in colorectal cancer therapy.
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As a transport channel for amino acids, solute carrier (SLC) exists in all kinds of cells, and its function is to transport various amino acids and provide necessary nutrients for the growth and development of cells. In recent years, SLC7A5 and SLC7A11 genes of SLC7 family members have been found to be highly expressed in various malignant tumors, which can promote the occurrence and development of tumors by providing necessary amino acids for tumors. Studies have shown that these genes are associated with a variety of malignant tumors, and their expression is closely related to the growth, metastasis, treatment and prognosis of tumor cells. Moreover, the results of multiple studies suggest that SLC7A5 and SLC7A11 genes can be used as therapeutic targets for malignant tumors. Clarifying the expression and clinical significance of the above genes in malignant tumors, the molecular biological mechanism and the progress of molecular targeted therapy are helpful to provide a new way for the diagnosis and treatment of malignant tumors.
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Neutrophils are the first to reach the site of infection as they are the most numerous and dominant pathogen-killing cells in the circulatory system. They are both involved in initial immunity and act as effector cells in destructive inflammatory responses. The abundance of neutrophils in the human body and their inherent properties give them the ability to target inflammatory sites for drug delivery, and their important role in the inflammatory response has led to increasing attention to the therapeutic potential of neutrophils. In this review paper, the research progress in neutrophil-mediated drug delivery systems is reviewed, including the use of neutrophils as carriers, neutrophil exosomes as carriers, and in vivo targeted delivery of drugs using neutrophil properties.
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@#Abstract: Objective To prepare a microparticle delivery system that regulates the release rate of extracellular vesicles (EVs), and to exert long-term enhancement of liver cell proliferation after only one intervention. Methods EVs was extracted by differential centrifugation. The structure of the EVs was observed by transmission electron microscopy and the membrane marker protein of EVs was detected by Western blotting. EVs-PLA microspheres with "core-shell" structure were prepared by emulsion-solvent evaporation method. Scanning and transmission electron microscopy were used to detect the morphology of EVs-PLA microspheres and EVs. The release test detected the release behavior of EVs in EVs-PLA microspheres. Scanning electron microscopy was used to detect the morphological changes of EVs-PLA microspheres at 8 weeks of release. EVs-PLA microspheres were co-cultured with hepatocytes, and Phalloidin/DAPI staining was used to observe the cell morphology and evaluate the cytotoxicity of the microspheres. CCK8-test was used to evaluate the cell proliferation activity. Western blot analysis was used to detect extracellular vesicles membrane marker protein expression. Results Comparing the ability of hepatocyte proliferation in the group treated with EVs-PLA microspheres and the control group, it was found that EVs-PLA microspheres did not cause cell apoptosis and mutation in cell structure, had biocompatibility and no cytotoxicity. The EVs-PLA microspheres with "core-shell" structure regulated the release behavior of EVs, which can continuously release EVs, exerting a continuous biological role in promoting hepatocyte proliferation after a single intervention. Conclusions The EVs-PLA microspheres can control-release EVs and promote hepatocyte proliferation continuously after a single intervention, providing a reference for further exploration of EVs-loaded delivery systems in promoting liver regeneration.
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Vesicles derived from Chinese medicinal herbs (VCMH) are nano-vesicular entities released by the cells of Chinese medicinal herbs. VCMHs have various biological effects and targeting characteristics, and their component chemicals and functional activities are closely related to the parent plant. VCMH differs from animal-derived vesicles in three ways: stability, specificity, and safety. There are a number of extraction and isolation techniques for VCMH, each with their own benefits and drawbacks, and there is no unified standard. When two or more approaches are used, high quantities of intact vesicles can be obtained more quickly and efficiently. The obtained VCMHs were systematically examined and evaluated. Firstly, they are generally saucer-shaped, cup-shaped or sphere, with particle size of 10-300 nm. Secondly, they contain lipids, proteins, nucleic acids and other active substances, and these components are an important part for intercellular information transfer. Finally, they mostly have good biocompatibility and low toxicity, with anti-inflammatory, antioxidant, anti-tumor and anti-fibrotic effects. As a new drug carrier, VCMHs have outstanding active targeting capabilities, and the capsule form can effectively preserve the drugs, considerably enhancing drug delivery efficiency and stability in vitro and in vivo. The modification of its vesicular structure by suitable physical or chemical means can further create more stable and precise drug carriers. This article reviews the extraction and purification techniques, activity evaluation and application of VCMH to provide information for further research and application of new active substances and targeted drug carriers.
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Animals , Drugs, Chinese Herbal/chemistry , Plants, Medicinal , Antioxidants , Anti-Inflammatory Agents , Drug CarriersABSTRACT
Currently, the first-line drugs for invasive fungal infections (IFI), such as amphotericin B, fluconazole and itraconazole, have drawbacks including poor water solubility, low bioavailability, and severe side effects. Using drug delivery systems is a promising strategy to improve the efficacy and safety of traditional antifungal therapy. Synthetic and biomimetic carriers have greatly facilitated the development of targeted delivery systems for antifungal drugs. Synthetic carrier drug delivery systems, such as liposomes, nanoparticles, polymer micelles, and microspheres, can improve the physicochemical properties of antifungal drugs, prolong their circulation time, enhance targeting capabilities, and reduce toxic side effects. Cell membrane biomimetic drug delivery systems, such as macrophage or red blood cell membrane-coated drug delivery systems, retain the membrane structure of somatic cells and confer various biological functions and specific targeting abilities to the loaded antifungal drugs, exhibiting better biocompatibility and lower toxicity. This article reviews the development of antifungal drug delivery systems and their application in the treatment of IFI, and also discusses the prospects of novel biomimetic carriers in antifungal drug delivery.
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Antifungal Agents/therapeutic use , Drug Delivery Systems , Amphotericin B/therapeutic use , Liposomes/chemistry , Nanoparticles , Drug CarriersABSTRACT
ObjectiveTo explore the inhibitory effect of different concentration of baicalin （0， 100， 200， 400 μmol·L-1） on the proliferation of human gastric cancer SGC-7901 cells and the underlying mechanism. MethodSGC-7901 cells were treated with baicalin. Then methyl thiazolyl tetrazolium （MTT） assay was employed to examine the inhibitory effect of baicalin on the cells. At the same time， ferrostatin-1 （Fer-1） was added to observe the viability of cells after baicalin treatment. The expression of ferroptosis-related genes was detected by Real-time polymerase chain reaction （Real-time PCR） and Western blot. The content of malondialdehyde （MDA） and the level of glutathione （GSH） were detected respectively by MTT assay and enzyme-linked immunosorbent assay. The role of tumor protein 53 （p53）/solute carrier family 7 member 11 （SLC7A11） pathway in the regulation of ferroptosis was investigated respectively via overexpression and small interfering RNA （siRNA） methods. ResultCompared with the blank group， baicalin decreased the viability of SGC-7901 （P<0.05， P<0.01） in a dose- and time-dependent manner. The intervention of Fer-1 significantly alleviated the decrease of SGC-7901 cell viability caused by baicalin （P<0.01）. In addition， compared with the baicalin group， Fer-1+baicalin group showed decrease in MDA content and the mRNA and protein levels of prostaglandin-endoperoxide synthase 2 （PTGS2） in the cells （P<0.01）， and increase in GSH activity and mRNA and protein levels of glutathione peroxidase 4 （GPX4） （P<0.01）. The protein level of SLC7A11 in the baicalin group was decreased compared with that in the blank group （P<0.05， P<0.01） in a dose-dependent manner. Compared with the baicalin group， the reactive oxygen species （ROS） level and MDA content in SLC7A11-overexpressing cells were significantly decreased after baicalin treatment （P<0.01）， and the GSH activity was significantly increased （P<0.01）. The fluorescence intensity of p53 in the cells of the baicalin group was increased compared with that of the blank group （P<0.01）. Compared with the baicalin group， the expression level of p53 protein in the cells transfected with p53 siRNA was significantly decreased after baicalin treatment （P<0.01）， and the expression level of SLC7A11 was significantly increased （P<0.01）. ConclusionBaicalin can effectively inhibit the proliferation of SGC-7901 cells by regulating p53/SLC7A11-mediated ferroptosis.
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As a natural drug delivery carrier with rough and porous surface and hollow core， yeast microcapsules have good safety， high targeting and high stability， and have excellent application prospects in oral drug delivery systems. Yeast cells can be treated and washed with acid-base and organic solvents to obtain loose and porous yeast microcapsules. Yeast microcapsules can encapsulate drugs through electrostatic interactions， passive diffusion， hydrophobic interaction and other methods. The surface of yeast microcapsules is mainly composed of β-glucan， which can maintain stability in the gastrointestinal environment； it can be recognized by the surface-related receptors of immune cells， thus activating the immune response， and can be transported to the lesion site with the movement of lymphocytes after being ingested. Yeast microcapsules are safe and very suitable for delivering vaccines， anti-inflammatory drugs， and anti-tumor drugs. They can not only achieve oral delivery of the aforementioned drugs， but also enhance drug efficacy and improve drug targeting. In the future， more research on systemic transport mechanisms or the development of more efficient combination drug delivery systems can be carried out to fully exhibit the clinical value of yeast microcapsules.
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With the rapid development of nanotechnology, the research and development of nanomedicines have become one of the development directions of drug innovation. Nanomedicines have special physical and chemical properties, such as nanoscale effects and nanostructure effects, so they have special biological properties, which may change the pharmacokinetic profiles such as absorption and tissue distribution of drug molecules, and thus affect their safety and effectiveness. There are many special concerns on the non-clinical safety evaluation of nanomedicines at the basis of ordinary drug because of the particularity of nanomedicines. On August 25, 2021, China issued Guidance on Non-clinical Safety Evaluation for Nanomedicines(interim). This article interprets comprehensively the guidance, focuses on the key points of non-clinical safety evaluation for nanomedicines, and expounds combined with some cases, aiming to provide reference for drug researchers.
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We constructed and optimized the plasmid DNA (pDNA) Opt-S encoding the gene of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein, using poly (lactic-co-glycolic acid) copolymer (PLGA) as a delivery carrier for pDNA. PLGA-pDNA NPs were loaded by nanoprecipitation and its properties in vitro were preliminary evaluated. The results showed that the prepared PLGA-pDNA NPs were regular morphology, clear edges, with an average particle size of (184.2 ± 2.4) nm, polydisperse index (PDI) of 0.093 ± 0.013, zeta potential of (-68.10 ± 0.36) mV, and encapsulation rate of (98.92 ± 0.22)%. The PLGA-pDNA NPs were stable at -20 ℃ for 7 months and could protect pDNA against nuclease degradation. And they also exhibited sustained release of pDNA in vitro. The PLGA-pDNA NPs have low cytotoxicity and high safety. In addition, in vitro transfection experiments showed that the SARS-CoV-2 S gene could enter cells and be expressed. These results indicate that PLGA-pDNA NPs non-viral gene vector have simple preparation process and good performance, which are expected to provide a new idea for the research and development of SARS-CoV-2 vaccine.
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Iontophoresis is a non-invasive physical permeation technology, which has been widely applied in transdermal and transmucosal administration. Compared with other permeation technologies, iontophoresis have the advantages of high efficacy, high patient compliance and controllable delivery dose. With the development of microneedles and nano-carrier technology, the combination of iontophoresis and other penetration promotion technologies has gradually become a research hotspot. The penetration mechanism and influencing factors of iontophoresis, and the study on the combination of iontophoresis with hydrogel, microneedles or nano-carrier were reviewed in this paper.
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ABSTRACT Background: Leptospirosis represents a One Health issue, affecting humans and animals. This study investigated pathogenic leptospires in small wild rodents in São Paulo, Brazil. Methods: Kidney samples from 164 rodents underwent qPCR testing, targeting pathogenic Leptospira spp. Results: Thirty-five animals (21.34%) tested positive, including five rodent species: Akodon montensis (2/21; 9.5%), Necromys lasiurus (1/4; 25%), Oligoryzomys nigripes (24/92; 26.1%), Oligoryzomys flavescens (5/26; 19.2%), and Sooretamys angouya (3/14; 21.4%). Botucatu municipality exhibited the highest prevalence, with 42.5% (20/47) of the animals testing positive. Conclusions: The presence of Leptospira spp. in wild rodents suggests they may be chronic carriers, contaminating the environment.
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Abstract Objective To estimate the frequency of Staphylococcus aureus and cephalosporin nonsusceptible bacteria colonization in patients with proximal femoral fracture during preoperative hospitalization. Methods Prevalence and incidence assessment in 63 hospitalized patients over 1 year. The median time of pretreatment hospitalization was 12 days. Samples were collected from the nostrils, groin skin and anal mucosa during the pretreatment hospitalization and were tested by the disc-diffusion technique. Results The hospital colonization incidence and the prevalence of positive results were 14.3 and 44.4% for S. aureus; 3.2 and 6.4% for meticillin-resistant S. aureus; 28.6 and 85.7% for meticillin-resistant coagulase-negative Staphylococcus; 28.6 and 61.9% for cefazolin nonsusceptible Enterobacteriaceae (KFNSE); and 20.6 and 28.6% for cefuroxime nonsusceptible Enterobacteriaceae (CXNSE). In addition, factors such as to the duration of the pretreatment hospitalization period, being non-walker before fracture, antimicrobial use, American Society of Anesthesiologists (ASA) 4 surgical risk, and previous hospitalization, were related to an increase in the incidence of hospital acquisition and prevalence of colonization by the evaluated strains. The prevalence of colonization by KFNSE was three times higher than by CXNSE on admission, and twice as high at the time of fracture treatment. Conclusion There was a high incidence of hospital colonization and prevalence of colonization by all strains studied, which may guide the indication of prophylactic measures for infection.
Resumo Objetivo Estimar a frequência da colonização por Staphylococcus aureus e as bactérias não suscetíveis à cefalosporina, em pacientes com fratura proximal do fêmur durante a internação pré-operatória. Métodos Avaliação da prevalência e incidência em 63 pacientes hospitalizados ao longo de um ano. O tempo médio de internação pré-tratamento foi de 12 dias. As amostras foram coletadas das narinas, pele da virilha e mucosa anal, durante a internação prévia ao tratamento e testadas pela técnica de disco-difusão. Resultados A incidência da colonização hospitalar e a prevalência de resultados positivos foram de 14,3% e 44,4% para Staphylococcus aureus; 3,2% e 6,4% para S. aureus resistente à meticilina; 28,6% e 85,7% para Staphylococcus coagulase-negativo resistente à meticilina; 28,6% e 61,9% para Enterobacteriaceae não suscetível à cefazolina (KFNSE); e 20,6% e 28,6% para Enterobacteriaceae não suscetível à cefuroxima (CXNSE). Além da duração do período de internação pré-tratamento, os pacientes não deambularam previamente à ocorrência da fratura e nem fizeram uso de antimicrobiano. Além disso, a duração do período de internação pré-tratamento cirúrgico, ser não-deambulador antes da fratura, uso de antimicrobianos, risco cirúrgico IV pela American Society of Anesthesiologists (ASA) e internação anterior, estiveram relacionados a um aumento na incidência de aquisição hospitalar e prevalência de colonização pelas cepas avaliadas. A prevalência de colonização pela KFNSE foi três vezes maior do que pela CXNSE na admissão e duas vezes maior no momento do tratamento da fratura. Conclusão Observou-se uma alta incidência da colonização hospitalar e prevalência da colonização por todas as cepas estudadas, o que pode orientar a indicação de medidas profiláticas contra a infecção.