DDS

DDS
  • 文章类型: Journal Article
    G4.0PAMAM树枝状聚合物的独特结构允许药物被封闭在内部空间或固定在表面上。在进行的研究中,优化了与盐酸多柔比星(DOX)形成活性G4.0PAMAM复合物的条件。使用动态光散射(DLS)监测系统的物理化学性质,圆二色性(CD),和荧光光谱。选择具有耗散监测的石英晶体微天平(QCM-D)方法来确定络合物形成的优选条件。当DOX分子去质子化时,在碱性条件下观察到药物与阳离子树枝状聚合物的最高结合效率。络合物的ζ电位的降低证实了DOX通过与载体的表面胺基的静电相互作用而固定。结合常数由在G4.0PAMAM存在下DOX分子的荧光猝灭确定。在等温量热法(ITC)等温线中可见树枝状分子结构中结合阿霉素的双重方式。荧光光谱和释放曲线确定了DOX与纳米载体的可逆结合。在选定的癌细胞中,在A375恶性黑色素瘤细胞中观察到G4.0-DOX复合物最有希望的抗癌活性。此外,发现了有关游离药物的复合物的优选细胞内位置,从治疗的角度来看,这是必不可少的。
    The unique structure of G4.0 PAMAM dendrimers allows a drug to be enclosed in internal spaces or immobilized on the surface. In the conducted research, the conditions for the formation of the active G4.0 PAMAM complex with doxorubicin hydrochloride (DOX) were optimized. The physicochemical properties of the system were monitored using dynamic light scattering (DLS), circular dichroism (CD), and fluorescence spectroscopy. The Quartz Crystal Microbalance with Dissipation Monitoring (QCM-D) method was chosen to determine the preferential conditions for the complex formation. The highest binding efficiency of the drug to the cationic dendrimer was observed under basic conditions when the DOX molecule was deprotonated. The decrease in the zeta potential of the complex confirms that DOX immobilizes through electrostatic interaction with the carrier\'s surface amine groups. The binding constants were determined from the fluorescence quenching of the DOX molecule in the presence of G4.0 PAMAM. The two-fold way of binding doxorubicin in the structure of dendrimers was visible in the Isothermal calorimetry (ITC) isotherm. Fluorescence spectra and release curves identified the reversible binding of DOX to the nanocarrier. Among the selected cancer cells, the most promising anticancer activity of the G4.0-DOX complex was observed in A375 malignant melanoma cells. Moreover, the preferred intracellular location of the complexes concerning the free drug was found, which is essential from a therapeutic point of view.
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  • 文章类型: Journal Article
    背景:这项研究使用饮食多样性评分(DDS)和饮食服务评分(DSS)调查了低食物多样性对儿童健康状况的影响。贫困家庭的百分比。通过分析食物多样性低的儿童的疾病成本,可以观察到食物多样性低的经济负担。
    方法:收集了329名儿童的数据。我们确定了DDS和DSS等因素对2-14岁儿童健康状况的影响,使用概率模型。疾病的费用(例如,斑疹伤寒,胃溃疡,咳嗽,流感,和发烧)由于食物多样性低,是从医疗登记费计算的,医疗行动费用,运输成本,和其他费用。
    结果:结果显示,DDS或DSS增加1%可能会使儿童的健康投诉减少10%和8%,分别。鉴于目前在低DDS儿童中26%的健康投诉患病率,每户儿童每年的经济负担达到75.72美元。此外,目前41%的低DDS儿童患病率导致政府为每名儿童每年花费153.45美元.
    结论:膳食多样性不足对儿童健康的影响可能很高,并导致家庭和政府的经济负担。
    BACKGROUND: This study investigates the impact of low food diversity on the health status of children using the Dietary Diversity Score (DDS) and Dietary Serving Score (DSS) in a sub-district with the highest percentage of poor households. The economic burden of low food diversity was observed by analysing the cost of illness in the children with low food diversity.
    METHODS: Data from 329 children were collected. We determined the impact of DDS and DSS and other factors on the health status of children aged 2-14 years, using a probit model. The cost of illness (e.g., typhus, stomach ulcers, coughs, flu, and fever) due to low food diversity was calculated from medical registration fees, medical action costs, transportation costs, and other costs.
    RESULTS: The results shows that a 1% point increase in DDS or DSS potentially decreases children\'s health complaints by 10% and 8%, respectively. Given the current 26% prevalence of health complaints among children with low DDS, the annual economic burden reaches US$75.72 per child per household. In addition, the current 41% prevalence of children with low DDS resulted in an annual cost to the government of US$153.45 per child.
    CONCLUSIONS: The effect of inadequate dietary diversity on children\'s health is potentially high and contributes to the economic burden on households and the government.
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  • 文章类型: Journal Article
    只有有限的研究调查饮食质量指标的影响,如膳食质量指数(DQI),膳食多样性评分(DDS),和替代健康饮食指数(AHEI),代谢功能障碍相关脂肪性肝病(MASLD)。此外,这些指标可能有不同的组成部分,可能导致不同的结果。因此,本研究旨在评估营养质量指标及其与MASLD的潜在关联.
    该研究包括128名最近诊断为MASLD的患者和256名年龄在20至60岁之间的对照。使用经过验证的半定量食物频率问卷评估参与者的饮食摄入量,该问卷由168个项目组成。在这项研究中,用于评估膳食多样性的方法基于五个主要食物组,特别是面包和谷物,蔬菜,水果,肉,和乳制品。AHEI-2010是使用从FFQ收集的数据计算的。
    在完全调整模型中对混杂因素进行调整后,DDS与MASLD风险呈显著负相关(OR0.41,95%CI0.20,0.97).在完全调整模型中控制了所有潜在的混杂因素后,AHEI前四分位数的参与者与下四分位数的参与者相比,MASLD的风险降低了76%(OR0.24,95%CI0.12,0.56)。
    我们的研究结果表明,坚持高多样性饮食与发展MASLD的可能性降低之间存在显着关联。同样,我们观察到坚持AHEI饮食与降低MASLD风险之间存在相似的关联.
    UNASSIGNED: There are only limited studies investigating the impact of dietary quality indicators, such as dietary quality index (DQI), dietary diversity score (DDS), and alternative healthy eating index (AHEI), on metabolic dysfunction-associated fatty liver disease (MASLD). Furthermore, these indicators may have different components that could lead to varying results. Therefore, this study aims to assess the nutritional quality indicators and their potential association with MASLD.
    UNASSIGNED: The study included 128 recently diagnosed MASLD patients and 256 controls aged between 20 and 60 years. The dietary intake of participants was evaluated using a validated semi-quantitative food frequency questionnaire that consisted of 168 items. In this study, the method used to evaluate dietary diversity was based on five main food groups, specifically bread and grains, vegetables, fruits, meat, and dairy. The AHEI-2010 was computed using data collected from the FFQ.
    UNASSIGNED: After adjusting for confounders in the fully adjusted model, a significant negative correlation was observed between DDS and the risk of MASLD (OR 0.41, 95% CI 0.20, 0.97). Participants in the top quartile of AHEI had a 76% lower risk of MASLD compared with those in the bottom quartile after controlling for all potential confounders in the fully adjusted model (OR 0.24, 95% CI 0.12, 0.56).
    UNASSIGNED: The results of our study suggest that there is a significant association between adherence to a high-diversity diet and a reduced likelihood of developing MASLD. Similarly, we observed a similar association between adherence to the AHEI diet and a lower risk of MASLD.
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  • 文章类型: Journal Article
    基于相位敏感和增强检测理论,锁定放大器(LIA)被广泛用于检测超弱光周期信号。在本文中,我们提出了一个全数字和通用的嵌入式LIA平台,准确,方便地描述了标准黑体在各种温度下使用不同的光学探测器产生的光谱。所提出的设计显著降低了传统模拟LIA的复杂性和成本,同时保持了准确性。LIA组件使用单个现场可编程门阵列(FPGA)实现。提供灵活性来修改不同情况下的参数。实验中捕获的光谱的归一化均方误差(NMSE)与理论值相比在0.9%以内。
    The lock-in amplifier (LIA) is widely utilized to detect ultra-weak optical periodic signals based on the phase-sensitive and enhanced detecting theory. In this paper, we present an all-digital and universal embedded LIA platform that accurately and conveniently describes the spectrum generated by standard black bodies at various temperatures with different optical detectors. The proposed design significantly reduces the complexity and cost of traditional analog LIAs while maintaining accuracy. The LIA components are implemented using a single field programmable gate array (FPGA), offering flexibility to modify parameters for different situations. The normalized mean-square error (NMSE) of the captured spectra in the experiments is within 0.9% compared the theoretical values.
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  • 文章类型: Journal Article
    药物递送系统(DDS)控制量,rate,和药物在体内的给药部位以及它们的释放和ADME(吸收,分布,新陈代谢,排泄)。在各种类型的DDS中,用于溶解和吸收的量控制的DDS增加了生物利用度。时间和数量受控的DDS是被分类为(1)膜型的控释制剂,(2)矩阵型,(3)渗透型,和(4)离子交换型。定时释放制剂还控制药物的释放和吸收的时间和量。位置和数量控制的DDS的特征在于结肠递送和肠淋巴靶向以改善药物物质的释放和ADME。最后,Site-,time-,和数量控制的DDS是胃滞留制剂和口腔局部递送,以改善部位保留,释放,和药物的ADME。DDS可以增强疗效,减少不利影响,并优化各种药物产品的给药频率,以增加患者价值。这篇综述的重点是推出口服DDS的患者价值和工业考虑因素。我们提供候选和上市DDS的技术概述,以及考虑到辅料的工业化技术的利弊,制造,和储存稳定性。此外,为了证明该技术的有用性,并支持为患者选择和开发最佳技术,我们还描述了来自临床研究和分析的患者价值,特别是关于增加新的医疗选择,更高的功效,减少不利影响,减少剂量和就诊次数,更容易管理,更高的生活质量,更大的坚持,和满意度。
    Drug delivery systems (DDS) control the amount, rate, and site of administration of drug substances in the body as well as their release and ADME (absorption, distribution, metabolism, excretion). Among the various types of DDS, amount-controlled DDS for solubilization and absorption increase the bioavailability. Time- and amount-controlled DDS are controlled release formulations classified as (1) membrane-type, (2) matrix-type, (3) osmotic-type, and (4) ion-exchange type. Timed-release formulations also control the time and amount of release and the absorption of drugs. Site- and amount-controlled DDS are characterized by colonic delivery and intestinal lymph-targeting to improve release and ADME of drug substances. Finally, site-, time-, and amount-controlled DDS are gastroretentive formulations and local delivery in the oral cavity to improve site retention, release, and ADME of drugs. DDS can enhance efficacy, reduce adverse effects, and optimize the dosing frequency of various drug products to increase patient value. This review focuses on patient value and industrial considerations of launched oral DDS. We provide a technological overview of candidate and marketed DDS, as well as the pros/cons of the technologies for industrialization with consideration to excipients, manufacturing, and storage stability. Moreover, to demonstrate the usefulness of the technology and support the selection and development of the best technologies for patients, we also describe patient value from clinical studies and analyses, particularly with regard to increased new medical options, higher efficacy, reduced adverse effects, reduced number of doses and clinic visits, easier administration, higher quality of life, greater adherence, and satisfaction.
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  • 文章类型: Journal Article
    脂滴(LD)是动态复杂的细胞器,参与各种生理过程,它们的数量和活动与多种疾病有关,包括癌症.在这项研究中,我们已经开发了基于查尔酮衍生物的LD特异性近红外(NIR)光响应纳米药物递送系统(DDSs),用于癌症治疗。报道的纳米DDS位于LD的癌症微环境中,暴露在光线下,他们以时空控制的方式递送抗癌药物丙戊酸。开发的系统,即,2'-羟基苯乙酮-二甲基氨基苯甲醛-丙戊酸(HA-DAB-VPA)和2'-羟基苯乙酮-二苯基氨基苯甲醛-丙戊酸(HA-DPB-VPA)酯缀合物,只需要两个简单的合成步骤。我们报道的DDS表现出有趣的特性,如激发态分子内质子转移(ESIPT)和聚集诱导发射(AIE)现象,它提供了诸如AIE引发的光释放和ESIPT增强的光释放速率等优点暴露于单或双光子光时。Further,通过使用两种癌细胞系(MCF-7细胞系和CT-26细胞系)和一种正常细胞系(HEK细胞系)对纳米DDS的共定位研究显示,LD浓度依赖性增强的荧光强度。此外,在细胞内存在和不存在油酸的情况下,对两种纳米DDS的系统研究表明,纳米DDSHA-DPB-VPA在LD中的积累更具选择性。nano-DDSHA-DPB-VPA对LD的这种独特选择性是由于二苯基氨基苯甲醛的疏水性(模仿LD核心),这显著导致聚集和ESIPT(在90%体积的fw,ΦF=20.4%,油酸ΦF=24.6%),分别。重要的是,我们将其用作光触发的抗癌药物递送模型,以利用LD内部纳米DDSHA-DPB-VPA的高选择性和积累。因此,这些发现为设计药物递送模型提供了原型,用于监测LD相关的细胞内活性并显着触发LD特异性药物在生物学领域的释放。
    Lipid droplets (LDs) are dynamic complex organelles involved in various physiological processes, and their number and activity are linked to multiple diseases, including cancer. In this study, we have developed LD-specific near-infrared (NIR) light-responsive nano-drug delivery systems (DDSs) based on chalcone derivatives for cancer treatment. The reported nano-DDSs localized inside the cancer microenvironment of LDs, and upon exposure to light, they delivered the anticancer drug valproic acid in a spatiotemporally controlled manner. The developed systems, namely, 2\'-hydroxyacetophenone-dimethylaminobenzaldehyde-valproic (HA-DAB-VPA) and 2\'-hydroxyacetophenone-diphenylaminobenzaldehyde-valproic (HA-DPB-VPA) ester conjugates, required only two simple synthetic steps. Our reported DDSs exhibited interesting properties such as excited-state intramolecular proton transfer (ESIPT) and aggregation-induced emission (AIE) phenomena, which provided advantages such as AIE-initiated photorelease and ESIPT-enhanced rate of photorelease upon exposure to one- or two-photon light. Further, colocalization studies of the nano-DDSs by employing two cancerous cell lines (MCF-7 cell line and CT-26 cell line) and one normal cell line (HEK cell line) revealed LD concentration-dependent enhanced fluorescence intensity. Furthermore, systematic investigations of both the nano-DDSs in the presence and absence of oleic acid inside the cells revealed that nano-DDS HA-DPB-VPA accumulated more selectively in the LDs. This unique selectivity by the nano-DDS HA-DPB-VPA toward the LDs is due to the hydrophobic nature of the diphenylaminobenzaldehyde (mimicking the LD core), which significantly leads to the aggregation and ESIPT (at 90% volume of fw, ΦF = 20.4% and in oleic acid ΦF = 24.6%), respectively. Significantly, we used this as a light-triggered anticancer drug delivery model to take advantage of the high selectivity and accumulation of the nano-DDS HA-DPB-VPA inside the LDs. Hence, these findings give a prototype for designing drug delivery models for monitoring LD-related intracellular activities and significantly triggering the release of LD-specific drugs in the biological field.
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  • 文章类型: Journal Article
    纳米结晶纤维素(NCC)因其表面积大等重要特性,在生物医学领域取得了突破,良好的机械强度,生物相容性,可再生性和掺入亲水性和疏水性物质的可行性。在本研究中,一些非甾体抗炎药(NSAID)的基于NCC的药物递送系统(DDS)是通过NCC的羟基与NSAID的羧基之间的共价键合获得的。开发的DDS通过FT-IR表征,XRD,SEM和热分析。体外释放研究和荧光研究表明,这些系统在pH1.2的上消化道(GI)中稳定长达18小时,并在pH6.8-7.4的肠道中持续3小时释放NSAID。本研究旨在重复使用生物废物,甚至以DDS的形式进行,具有更大的治疗效果,减少了给药频率,克服了NSAID涉及的生理逆境。
    Nano crystalline cellulose (NCC) created a breakthrough in biomedical field because of its important characteristics like large surface area, good mechanical strength, biocompatibility, renewability and feasibility of incorporation to both hydrophilic and hydrophobic substances. In the present study NCC based drug delivery systems (DDSs) of some non-steroidal anti-inflammatory drugs (NSAIDs) were obtained by covalent bonding between hydroxyl groups of NCC with carboxyl group of NSAIDs. Developed DDSs were characterized by means of FT-IR, XRD, SEM and thermal analysis. In-vitro release study and fluorescence study showed that these systems are stable up to 18 h in upper gastrointestinal (GI) tract at pH 1.2 and released NSAIDs in sustained manner over the period of 3 h in intestine at pH 6.8-7.4. Present study performed with the aim to reuse bio-waste even in the form of DDSs is of greater therapeutic efficacy with reduced dosing frequency that overcome physiological adversities involved with NSAIDs.
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  • 文章类型: Journal Article
    这篇简短综述的重点是描述纳米粒子的应用,包括内源性纳米颗粒(例如,细胞外囊泡,电动汽车,和病毒衣壳)和外源纳米颗粒(例如,有机和无机材料)在癌症治疗和诊断中。在这次审查中,我们主要关注电动汽车,最近的一项研究表明,癌细胞分泌的电动汽车与癌症的恶性改变有关。电动汽车有望通过分析其信息货物来用于癌症诊断。外源纳米颗粒也用于癌症诊断作为成像探针,因为它们可以很容易地功能化。纳米颗粒是药物递送系统(DDS)开发的有希望的靶标,最近已被积极研究。在这次审查中,我们介绍纳米粒子作为癌症治疗和诊断领域的强大工具,并讨论问题和未来前景。
    The focus of this brief review is to describe the application of nanoparticles, including endogenous nanoparticles (e.g., extracellular vesicles, EVs, and virus capsids) and exogenous nanoparticles (e.g., organic and inorganic materials) in cancer therapy and diagnostics. In this review, we mainly focused on EVs, where a recent study demonstrated that EVs secreted from cancer cells are associated with malignant alterations in cancer. EVs are expected to be used for cancer diagnostics by analyzing their informative cargo. Exogenous nanoparticles are also used in cancer diagnostics as imaging probes because they can be easily functionalized. Nanoparticles are promising targets for drug delivery system (DDS) development and have recently been actively studied. In this review, we introduce nanoparticles as a powerful tool in the field of cancer therapy and diagnostics and discuss issues and future prospects.
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  • 文章类型: Journal Article
    包封治疗剂的外泌体用于治疗疾病的用途越来越令人感兴趣。然而,一些问题,例如常规药物包封方法对外泌体的效率有限和可扩展性仍然存在;因此,需要一种能够以优异的效率和可扩展性封装治疗剂的新方法。在这里,我们使用RAW264巨噬细胞衍生的外泌体(RAW-Exos),并证明使用微流化器的高压均质化(HPH)在不改变其形态的情况下降低了其粒径,外泌体标记蛋白的数量,以及RAW264和结肠癌细胞的细胞摄取效率。此外,HPH允许将聚乙二醇(PEG)缀合的脂质修饰到RAW-Exos上,以及抗癌剂阿霉素的封装。重要的是,在增加工艺压力和同时使用PEG-脂质的HPH时,阿霉素包封效率变得更高。此外,用PEG修饰的RAW-Exos封装阿霉素的治疗显著抑制了携带结肠-26小鼠的肿瘤生长。一起来看,这些结果表明,使用微流化器的HPH可用于通过一步制药工艺制备PEG修饰的Exos封装抗癌药物,制备的功能性Exos可用于体内治疗癌症。
    The use of exosomes encapsulating therapeutic agents for the treatment of diseases is of increasing interest. However, some concerns such as limited efficiency and scalability of conventional drug encapsulation methods to exosomes have still remained; thus, a new approach that enables encapsulation of therapeutic agents with superior efficiency and scalability is required. Herein, we used RAW264 macrophage cell-derived exosomes (RAW-Exos) and demonstrated that high-pressure homogenization (HPH) using a microfluidizer decreased their particle size without changing their morphology, the amount of exosomal marker proteins, and cellular uptake efficiency into RAW264 and colon-26 cancer cells. Moreover, HPH allowed for modification of polyethylene glycol (PEG)-conjugated lipids onto RAW-Exos, as well as encapsulation of the anti-cancer agent doxorubicin. Importantly, the doxorubicin encapsulation efficiency became higher upon increasing the process pressure and simultaneous HPH with PEG-lipids. Moreover, treatment with PEG-modified RAW-Exos encapsulating doxorubicin significantly suppressed tumor growth in colon-26-bearing mice. Taken together, these results suggest that HPH using a microfluidizer could be useful to prepare PEG-modified Exos encapsulating anti-cancer drugs via a one-step pharmaceutical process, and that the prepared functional Exos could be applied for the treatment of cancer in vivo.
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  • 文章类型: Journal Article
    由于其独特的结构,聚(酰胺基胺)(PAMAM)树枝状聚合物可以以两种方式结合活性成分:在结构内部或在其表面上。药物分子的位置显着影响活性物质释放的动力学和内化到细胞中的机制。这项研究的重点是G4PAMAM树枝状聚合物和抗癌药物5-氟尿嘧啶(5FU)的质子化程度对复合物形成效率的影响。构建G4PAMAM-5FU复合物的最有利条件是树枝状聚合物分子的低程度的质子化,其中药物同时以去质子化形式存在。XPS光谱中的氟组分证实了稳定络合物的形成。通过SAXS和DLS方法,证明了在碱性条件下质子化变化导致的树枝状聚合物分子大小的减小。在高pH值下观察到的树枝状聚合物结构的逐渐闭合使得5FU分子难以迁移到支撑结构的内部,从而促进药物在表面上的固定。1HNMR和DOSY光谱表明静电相互作用决定了络合物的形成过程。通过MD模拟,在原子尺度上可视化了形成复合物的5FU分子的定位谱和数量。
    Due to their unique structure, poly(amidoamine) (PAMAM) dendrimers can bind active ingredients in two ways: inside the structure or on their surface. The location of drug molecules significantly impacts the kinetics of active substance release and the mechanism of internalization into the cell. This study focuses on the effect of the protonation degree of the G4PAMAM dendrimer and the anticancer drug 5-fluorouracil (5FU) on the efficiency of complex formation. The most favorable conditions for constructing the G4PAMAM-5FU complex are a low degree of protonation of the dendrimer molecule with the drug simultaneously present in a deprotonated form. The fluorine components in the XPS spectra confirm the formation of the stable complex. Through SAXS and DLS methods, a decrease in the dendrimer\'s molecular size resulting from protonation changes at alkaline conditions was demonstrated. The gradual closure of the dendrimer structure observed at high pH values makes it difficult for the 5FU molecules to migrate to the interior of the support structure, thereby promoting drug immobilization on the surface. The 1H NMR and DOSY spectra indicate that electrostatic interactions determine the complex formation process. Through MD simulations, the localization profile and the number of 5FU molecules forming the complex were visualized on an atomic scale.
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