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1.
Nano carriers have greatly revolutionized the treatment of most diseases recently. One of these nano carriers, liposomes, has got particular significance. On the other hand, Artemisinin which is used as an effective anticancer drug has some side effects. To reduce such side effects, liposomes can be employed. In order to prepare pegylated nanoliposomal artemisinin, particular proportions of phosphatidylcholine, polyethylene glycol 2000 and artemisinin were combined. As a result, the mean diameter of nano liposomes is 455 nm. Besides, the encapsulation efficiency and the drug release from pegylated nanoliposomes for pegylated nanoliposomal artemisinin are respectively 91.62 ± 3.5 and 5.17 %. The results also show that IC50 of the produced formulation is less than that of the standard drug. This study reveals that the amount of artemisinin cytotoxicity compared to standard drug is increased by pegylated nanoliposomal formulation.  相似文献   

2.
Breast cancer is one of the most frequent cancer types within women population. Hydroxyurea (HU) is a chemotherapy compound for treatment of patients with cancer diagnosis, including breast cancer associated with several adverse effects. In this study, we applied nanotechnology to decreased drug side effects along with improvement of therapeutic index. Liposomation is widely used in modern pharmacological developments in order to enhance the effects of the drugs. To achieve this, in this study a mixture of phosphatidylcholine and cholesterol was made up and HU was added to the resultant mixture, was then pegylated using Polyethylene Glycol 2000 to increase resistance, applicability and solubility. The mean diameters of nanoliposomal and pegylated nanoliposomal HU were measured by Zeta sizer device and obtained about 402.5 and 338.2 nm. The efficiency of non-pegylated and pegylated liposomal HU was 70.8 and 64.2, respectively. Releasing HU in both formulations was estimated about 25.8 and 21.7 %. Also, this study investigated the cytotoxicity effect of nanoliposomal and pegylated nanoliposomal HU using MTT assay. Results of this investigation showed that the cytotoxic properties of pegylated HU was 3.6 % more than those non-pegylated form, while was 38.93 % more than ordinary from of HU. This study showed that the stability, releasing pattern and cytotoxicity of the pegylated nanoliposomal HU is better than that of nanoliposomal HU.  相似文献   

3.
Regarding that the breast cancer is the most prevalent disease among women, paclitaxel, an anti-cancer drug, could be used in treatment of this disease. As paclitaxel has adverse effects, it was used of nanoliposome drug delivery technology in order to reduce adverse effects and improve drug efficacy. Certain ratios of phosphatidylcholine, cholesterol and paclitaxel were synthesized to prepare nanoliposomal paclitaxel. Using Zeta sizer device, the mean diameter of nanoliposomal paclitaxel was obtained 421.4 nm and its encapsulation efficiency was 91.3 %. By dialysis, drug release in nanoliposome paclitaxel formulation within 28 h was studied which was 5.53 %. This study showed that cytotoxicity effect of nanoliposomal paclitaxel is more than that of the standard form.  相似文献   

4.
It is clear that cancer is one of the most mortal diseases in the world and the most prevalent among women is breast cancer. As hydroxyurea (HU)—a drug which is used in chemotherapy—has many adverse effects in long-term despite of its therapeutic properties, we made use of nano drug delivery technology in order to reduce adverse effects and increase therapeutic index. Thus, liposomation is a novel way in drug delivery systems. In this study a mixture of phosphatidylcholine and cholesterol was mixed and HU was added to the resultant mixture. The mean diameter of the nanoliposomal HU measured with the Zeta Sizer device (equal to 402.5 nm) and its encapsulation efficiency was 70.8 %. Besides, using dialysis, the pattern of drug release from nanoliposomes has been studied and the results showed that the drug release of nanoliposomal drug within 28 h was equal to 25.85 %. This study showed that the cytotoxicity effect of nanoliposomal drug is more than that of the standard drug.  相似文献   

5.
Carboplatin is a chemotherapeutic agent used against various malignancies such as ovarian carcinoma. The aim of this study is to improve the therapeutic efficacy of carboplatin using pegylated liposomal nanocarriers. Nanoparticles were synthesized using thin film hydration technique and characterized for shape morphology, particle size, zeta potential and drug-release properties. In the next step, A2780S and A2780CP ovarian cancer cell lines were used to determine the efficacy of nanodrug by MTT assay. The particle size and zeta potential of nanodrug were measured 244.3 ± 19.6 nm and ?22.9 ± 1.7 mV, respectively. High encapsulation capacity (78.6 ± 3.7 %) confirmed the efficiency of technique. The cytotoxicity results also showed that nanodrug compared to free drug improve the efficacy of carboplatin against both A2780S (P < 0.01) and A2780CP (P < 0.05) cell lines. In conclusion, the findings of our study suggested pegylated liposomal nanocarriers are proper for carboplatin delivery to ovarian cancer cell lines A2780S and A2780CP.  相似文献   

6.
In the present study, paclitaxel was archaeosomed to reduce side effects and improve its therapeutic index. Carriers have made a big evolution in treatment of many diseases in recent years. Lipid carriers are of special importance among carriers. Archaeosome is one of the lipid carriers. Paclitaxel is one of the drugs used to treat breast cancer which has some unwanted side effects despite its therapeutic effects. Archaeosomes were extracted from methanogenic archi bacteria and synthesized with a certain ratio of paclitaxel in PBS. The mean diameter of archaeosomal paclitaxel was measured by Zeta sizer instrument, Drug releasing of archaeosomal paclitaxel was examined within 26 h which results showed that the most drug releasing occurs during first 3 h. The cytotoxicity effect of archaeosomal paclitaxel on breast cancer’s cell line was evaluated by MTT assay which results showed that the cytotoxicity effect of archaeosomal paclitaxel on breast cancer’s cell line is more than that of the standard paclitaxel formulation. The results indicated that new drug delivery of paclitaxel using archaeosome, increases the therapeutic index of the drug.  相似文献   

7.
青蒿素:从中国传统药方到全球抗疟良药   总被引：1，自引：0，他引：1       下载免费PDF全文
青蒿素是从中国传统药物青蒿中提取的抗疟药物。青蒿素及其衍生物、复方的应用为全球疟疾耐药性难题提供了有效的解决方案。青蒿素及其衍生物作为全球疟疾治疗的首选药物,解除了数百万疟疾患者的病痛,因此在青蒿素研制中作出了突出贡献的屠呦呦成为因为在中国本土进行的科学研究而首次获诺贝尔科学奖的中国科学家。青蒿素的发现是在一个特殊的社会文化环境中完成的,是一个任务("523任务")带动科研和学科发展的典型案例,是国家需要与科学研究相互促进的结果。文章回顾青蒿素研发的历史,考察在设备、技术条件相对落后的情况下,如何通过有组织的科研协作、多机构的优势整合而取得突破的经验,探讨社会、政治、文化与基础研究、开发应用之间的互动关系,从中汲取经验与教益。  相似文献   

8.
Intracellular drug delivery by rapid squeezing is one of the most recent and simple cell membrane disruption-mediated drug encapsulation approaches. In this method, cell membranes are perforated in a microfluidic setup due to rapid cell deformation during squeezing through constricted channels. While squeezing-based drug loading has been successful in loading drug molecules into various cell types, such as immune cells, cancer cells, and other primary cells, there is so far no comprehensive understanding of the pore opening mechanism on the cell membrane and the systematic analysis on how different channel geometries and squeezing speed influence drug loading. This article aims to develop a three-dimensional computational model to study the intracellular delivery for compound cells squeezing through microfluidic channels. The Lattice Boltzmann method, as the flow solver, integrated with a spring-connected network via frictional coupling, is employed to capture compound capsule dynamics over fast squeezing. The pore size is proportional to the local areal strain of triangular patches on the compound cell through mathematical correlations derived from molecular dynamics and coarse-grained molecular dynamics simulations. We quantify the drug concentration inside the cell cytoplasm by introducing a new mathematical model for passive diffusion after squeezing. Compared to the existing models, the proposed model does not have any empirical parameters that depend on operating conditions and device geometry. Since the compound cell model is new, it is validated by simulating a nucleated cell under a simple shear flow at different capillary numbers and comparing the results with other numerical models reported in literature. The cell deformation during squeezing is also compared with the pattern found from our compound cell squeezing experiment. Afterward, compound cell squeezing is modeled for different cell squeezing velocities, constriction lengths, and constriction widths. We reported the instantaneous cell center velocity, variations of axial and vertical cell dimensions, cell porosity, and normalized drug concentration to shed light on the underlying physics in fast squeezing-based drug delivery. Consistent with experimental findings in the literature, the numerical results confirm that constriction width reduction, constriction length enlargement, and average cell velocity promote intracellular drug delivery. The results show that the existence of the nucleus increases cell porosity and loaded drug concentration after squeezing. Given geometrical parameters and cell average velocity, the maximum porosity is achieved at three different locations: constriction entrance, constriction middle part, and outside the constriction. Our numerical results provide reasonable justifications for experimental findings on the influences of constriction geometry and cell velocity on the performance of cell-squeezing delivery. We expect this model can help design and optimize squeezing-based cargo delivery.  相似文献   

9.
Droplet-based microfluidics has shown potential in high throughput single cell assays by encapsulating individual cells in water-in-oil emulsions. Ordering cells in a micro-channel is necessary to encapsulate individual cells into droplets further enhancing the assay efficiency. This is typically limited due to the difficulty of preparing high-density cell solutions and maintaining them without cell aggregation in long channels (>5 cm). In this study, we developed a short pinched flow channel (5 mm) to separate cell aggregates and to form a uniform cell distribution in a droplet-generating platform that encapsulated single cells with >55% encapsulation efficiency beating Poisson encapsulation statistics. Using this platform and commercially available Sox substrates (8-hydroxy-5-(N,N-dimethylsulfonamido)-2-methylquinoline), we have demonstrated a high throughput dynamic single cell signaling assay to measure the activity of receptor tyrosine kinases (RTKs) in lung cancer cells triggered by cell surface ligand binding. The phosphorylation of the substrates resulted in fluorescent emission, showing a sigmoidal increase over a 12 h period. The result exhibited a heterogeneous signaling rate in individual cells and showed various levels of drug resistance when treated with the tyrosine kinase inhibitor, gefitinib.  相似文献   

10.
We report a method for formulation of pectin microbeads using microfluidics. The technique uses biocompatible ingredients and allows for controlled external gelation with hydrogen and calcium ions delivered from an organic phase of rapeseed oil. This method allows for encapsulation of nanoparticles into the microparticles of gel and for control of the rate of their release.  相似文献   

11.
Biosynthetic microspheres have the potential to address some of the limitations in cell microencapsulation; however, the generation of biosynthetic hydrogel microspheres has not been investigated or applied to cell encapsulation. Droplet microfluidics has the potential to produce more uniform microspheres under conditions compatible with cell encapsulation. Therefore, the aim of this study was to understand the effect of process parameters on biosynthetic microsphere formation, size, and morphology with a co-flow microfluidic method. Poly(vinyl alcohol) (PVA), a synthetic hydrogel and heparin, a glycosaminoglycan were chosen as the hydrogels for this study. A capillary-based microfluidic droplet generation device was used, and by varying the flow rates of both the polymer and oil phases, the viscosity of the continuous oil phase, and the interfacial surface tension, monodisperse spheres were produced from ∼200 to 800 μm. The size and morphology were unaffected by the addition of heparin. The modulus of spheres was 397 and 335 kPa for PVA and PVA/heparin, respectively, and this was not different from the bulk gel modulus (312 and 365 for PVA and PVA/heparin, respectively). Mammalian cells encapsulated in the spheres had over 90% viability after 24 h in both PVA and PVA/heparin microspheres. After 28 days, viability was still over 90% for PVA-heparin spheres and was significantly higher than in PVA only spheres. The use of biosynthetic hydrogels with microfluidic and UV polymerisation methods offers an improved approach to long-term cell encapsulation.  相似文献   

12.
BackgroundSuper-paramagnetic iron oxide nanoparticles (SPION) contain a chemotherapeutic drug and are regarded as a promising technique for improving targeted delivery into cancer cells.ResultsIn this study, the fabrication of 5-fluorouracil (5-FU) was investigated with loaded Dextran (DEX-SPION) using the co-precipitation technique and conjugated by folate (FA). These nanoparticles (NPs) were employed as carriers and anticancer compounds against liver cancer cells in vitro. Structural, magnetic, morphological characterization, size, and drug loading activities of the obtained FA-DEX-5-FU-SPION NPs were checked using FTIR, VSM, FESEM, TEM, DLS, and zeta potential techniques. The cellular toxicity effect of FA-DEX-5-FU-SPION NPs was evaluated using the MTT test on liver cancer (SNU-423) and healthy cells (LO2). Furthermore, the apoptosis measurement and the expression levels of NF-1, Her-2/neu, c-Raf-1, and Wnt-1 genes were evaluated post-treatment using flow cytometry and RT-PCR, respectively. The obtained NPs were spherical with a suitable dispersity without noticeable aggregation. The size of the NPs, polydispersity, and zeta were 74 ± 13 nm, 0.080 and −45 mV, respectively. The results of the encapsulation efficiency of the nano-compound showed highly colloidal stability and proper drug maintenance. The results indicated that FA-DEX-5-FU-SPION demonstrated a sustained release profile of 5-FU in both phosphate and citrate buffer solutions separately, with higher cytotoxicity against SNU-423 cells than against other cells types. These findings suggest that FA-DEX-SPION NPs exert synergistic effects for targeting intracellular delivery of 5-FU, apoptosis induction, and gene expression stimulation.ConclusionsThe findings proved that FA-DEX-5-FU-SPION presented remarkable antitumor properties; no adverse subsequences were revealed against normal cells.How to cite: Mahdia SA, Kadhimb AA, Albukhaty S, et al. Gene expression and apoptosis response in hepatocellular carcinoma cells induced by biocompatible polymer/magnetic nanoparticles containing 5-fluorouracil. Electron J Biotechnol 2021;52. https://doi.org/10.1016/j.ejbt.2021.04.001  相似文献   

13.
The bystander effect in cancer therapy is the inhibition or killing of tumor cells that are adjacent to those directly affected by the agent used for treatment. In the case of chemotherapy, little is known as to how much and by which mechanisms bystander effects contribute to the elimination of tumor cells. This is mainly due to the difficulty to distinguish between targeted and bystander cells since both are exposed to the pharmaceutical compound. We here studied the interaction of tamoxifen-treated human breast cancer MCF-7 cells with their neighboring counterparts by exploiting laminar flow patterning in a microfluidic chip to ensure selective drug delivery. The spatio-temporal evolution of the bystander response in non-targeted cells was analyzed by measuring the mitochondrial membrane potential under conditions of free diffusion. Our data show that the bystander response is detectable as early as 1 hour after drug treatment and reached effective distances of at least 2.8 mm. Furthermore, the bystander effect was merely dependent on diffusible factors rather than cell contact-dependent signaling. Taken together, our study illustrates that this microfluidic approach is a promising tool for screening and optimization of putative chemotherapeutic drugs to maximize the bystander response in cancer therapy.  相似文献   

14.
Drug protein binding phenomena can lead to some interesting drug—drug interactions when one drug displaces another in the binding site. Studies of protein binding are conducted by several methods including equilibrium dialysis, ultra-filtration and chromatographic methods. Gel filtration is a simple chromatographic method in protein binding studies. Propranolol binds to plasma proteins by 90%–95% in circulation system and other drugs with high protein binding may displace it. In this study protein binding of propranolol has been studied using gel filtration to Bovine Serum Albumin (BSA) alone and in the presence of Acetyl salicylic acid (ASA), Indomethacin and mefenamic acid has been studied using gel filtration method. The results indicated that ASA decreased protein binding of propranolol by 20% to BSA and other drugs did not displace propranolol from the binding site. Therefore, ASA may alter pharmacological effects of propranolol.  相似文献   

15.
为探索一种对大量因素同时进行定量分析的方法,尝试采用对高纬稀疏数据进行分析,对沪深两市制造型企业进行分析,以研发投入强度达到3. 5%以上为分析目标,并得到达到这一分析目标的定量优化规则,当收入熵小于0. 579 4、销售毛利率适中(17. 5%~29. 54%)、董事职能背景差异小于0. 399 5、前10大股东持股比例适中(0. 168 9~0. 665 7),企业研发投入强度达到分析目标的比例会大幅提升。这一分析方法既可以用于国有高新技术企业经营层、董事会人员配置作为参考,又可作为对企业研发投入行为的预判。  相似文献   

16.
徐朝辉  周宗放 《科研管理》2016,37(9):136-144
管理者的非理性行为—"过度自信"不仅影响企业多元化经营战略,且可能加剧企业信用风险。本文从行为科学视角,对管理者过度自信与经营多元化之间的关系及其对信用风险的影响进行了深入分析,并以深沪A股2009-2012年间的上市公司为研究对象进行了实证检验。研究发现管理者过度自信与多元化经营程度显著正相关,与信用风险显著正相关,多元化经营在管理者过度自信与信用风险之间存在显著中介效应。同时,前期多元化经营程度显著正向影响管理者过度自信心理,而前期企业信用风险对管理者过度自信心理影响不显著。本文的研究结果对企业管理者自身行为修正与经营战略制订具有一定的参考价值。  相似文献   

17.
Cisplatinum (Cispt) is an anti-cancer drug with a low level of solubility. One of Cispt’s solvents is dimethyl sulfoxide (DMSO) which can be substituted with chlorine of drug as Cispt’s solvent. Applying such a solvent in biological studies is impossible due to intense reduction in activity. On the other hand, it is specified that Cispt’s stability is increased in aqueous media by increasing sodium chloride (NaCl) concentration up to 0.9 %. Consequently, we intended to study the effect of DMSO on cytotoxicity of Cispt in presence of sodium. MTT assay was employed to study cytotoxicity effect of Cispt + NaCl + DMSO and Cispt + DMSO on G-292 cell line. Cytotoxicity in dilutions of 300 and 9 (p < 0.01) of Cispt in Cispt + NaCl + DMSO formulation was equal to 78 and 7 %. These values were estimated 79 and 18 % for Cispt + DMSO formulation and 79 and 24 % for free drug. IC50 values demonstrated reduction of 45 % in cytotoxicity of Cispt in Cispt + DMSO formulation. Studying chemical structure of Cispt and Cispt dissolved in DMSO showed that NaCl cannot inhibit inactivating effect of DMSO on Cispt and effect of this solvent on Cispt is independent from presence of NaCl. Results represented that using NaCl does not result in stability and keeping cytotoxicity properties of Cispt in DMSO. Findings suggest more studies for using DMSO as a solvent of Cispt.  相似文献   

18.
宋巧枝  方曙 《现代情报》2007,27(10):193-195
当前经济的发展越来越倚重于科技水平的提升，能够较全面完整地反映科技发展、特别是技术发展态势的专利信息就日渐成为重要的情报来源，专利信息分析也因而在战略制定中发挥着日益重要的作用。本文在介绍战略制定基础知识及其相关专利分析指标的基础上，从企业的角度，基于外部分析、内部分析以及战略类型分析这三方面来讨论专利信息分析方法在战略制定中的应用。  相似文献   

19.
国内外学者对科研投入与企业绩效之间的关系进行了大量研究和实证工作,现有研究多以定性研究为主,分析研发投入与企业绩效之间的关系以及影响这两者关系的直接和间接变量,有少量学者用定量分析的方法表达某个或者某几个变量与这两者关系之间的数学关系,但由于企业绩效及科研成果结果显现的影响变量太多,这种定量分析方法的局限性大。为探索一种对大量因素同时进行定量分析的方法,尝试采用对高纬稀疏数据进行分析,对沪深两市327家制造企业2011~2016年的数据进行分析,以“研发投入增长率>0 & 营业收入增长率>0 & 人均营业收入增长率>0”为分析目标,对影响目标实现的十类74个变量进行定量分析,并得到达到这一分析目标的定量优化规则：当期和上期单位研发人员研发投入、研发人员投入增长率、盈利能力、产品市场竞争度这五个变量处于一定范围内时,分析目标达成概率有较大幅度提升。这一分析结果既可以用于衡量企业研发水平是否达到规模边界,又可作为对企业研发投入行为对企业绩效结果的预判。  相似文献   

20.
樊莉 《科教文汇》2014,(12):224-225
目前电信工程类企业的工时和考勤管理越来越关注工时效率。为提高劳动生产率和工时利用率,本文提出了工时管理三项指标体系,论述了其实施背景、推行的具体措施以及配套措施,并结合推行实例探讨了其分析方法。  相似文献   

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