Microparticle

微粒
  • 文章类型: Journal Article
    使用立体显微镜鉴定了半封闭大阪湾海水中的人为颗粒,使用傅里叶变换红外光谱(FTIR)根据聚合物类型进行分类,并根据他们的身体特征进行分类。在水样中检测到总共565.1个颗粒。然而,塑料颗粒仅占颗粒的22.4%。大阪湾的微塑料丰度显示出从8.9±1.4(5月)到22.8±6.5颗粒/L(7月)的季节性变化,这与以前在其他半封闭海湾的报告一致。微塑料主要呈碎片状和纤维状,灰色和无色/白色着色。主要的聚合物类型是聚丙烯,聚(甲基丙烯酸甲酯),聚酯,聚乙烯,和聚对苯二甲酸乙二醇酯。一般来说,与近岸地点相比,海上地点的微塑料丰度要高得多。这项研究的结果表明,当地的河流废水和与海洋有关的活动可能是大阪湾微塑料的来源。
    Anthropogenic particles in sea surface water of the semi-enclosed Osaka Bay were identified using stereomicroscopy, classified according to polymer type using Fourier-transform infrared spectroscopy (FTIR), and categorized according to their physical characteristics. A total of 565.1 particles were detected in the water samples. However, plastic particles accounted for only 22.4% of the particles. Microplastic abundance in Osaka Bay showed seasonal variance from 8.9 ± 1.4 (in May) to 22.8 ± 6.5 particles/L (in July), which is consistent with previous reports in other semi-enclosed bays. Microplastics were mainly fragmented and fiber shaped, with gray and colorless/white coloration. The dominant polymer types were polypropylene, poly(methylmethacrylate), polyester, polyethylene, and polyethylene terephthalate. Generally, there were considerably higher abundances of microplastics at offshore sites compared with nearshore sites. The results of this study suggest that local river effluents and marine-related activities are probable sources of microplastics in Osaka Bay.
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  • 文章类型: Journal Article
    微球已经作为创新的药物递送平台出现,其具有显著的潜力来改善具有有限水溶性的药物的治疗功效并延长其释放。本摘要概述了微球研究的最新进展,突出关键趋势和创新方法。最近的研究集中在微球的各个方面,包括配方技术,材料选择,以及它们在药物输送中的应用。聚合物科学最近的突破为创造创新的可生物降解和生物相容性材料用于微球制造铺平了道路。提高药物包封效果和释放动力学。值得注意的是,纳米材料和官能化聚合物的整合使得能够精确控制药物释放速率并增强靶向能力。使用微球来施用各种治疗物质,包括抗癌药物,抗炎药,和肽,获得了极大的关注。这些微球已经证明了增强药物稳定性的潜力,尽量减少给药频率,提高患者依从性。
    Microspheres have emerged as innovative drug delivery platforms with significant potential to improve the therapeutic efficacy of drugs with limited aqueous solubility and prolong their release. This abstract provides an overview of recent developments in microsphere research, highlighting key trends and innovative approaches. Recent studies have focused on various aspects of microspheres, including formulation techniques, materials selection, and their applications in drug delivery. Recent breakthroughs in polymer science have paved the way for the creation of innovative biodegradable and biocompatible materials for microsphere fabrication, improving drug encapsulation effectiveness and release dynamics. Notably, the integration of nanomaterials and functionalized polymers has enabled precise control over drug release rates and enhanced targeting capabilities. The utilization of microspheres for administering a diverse array of therapeutic substances, including anticancer drugs, anti-inflammatory agents, and peptides, has gained significant attention. These microspheres have demonstrated the potential to enhance drug stability, minimize dosing frequency and enhance patient adherence.
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  • 文章类型: Journal Article
    双水相体系(ATPS)是两个水相之间的液-液平衡,每个水相通常含有超过70%的水含量,这导致对生物化合物和生物分子无毒的无有机溶剂环境。ATPS在配制载体(微粒,纳米粒子,水凝胶,和聚合物囊泡),可以使用ATPS的自发相分离作为驱动力来制备,装载了各种各样的生物活性材料,包括小分子药物,蛋白质,和细胞,用于交付应用程序。这篇综述详细分析了各种ATPS,包括用于粒子形成的策略,ATPS中液滴的聚合,相引导嵌段共聚物组件,和刺激响应载体。讨论了加载各种生物活性有效载荷的过程,并对这些给药系统的应用进行了总结和讨论。
    Aqueous two-phase systems (ATPSs) are liquid-liquid equilibria between two aqueous phases that usually contain over 70% water content each, which results in a nontoxic organic solvent-free environment for biological compounds and biomolecules. ATPSs have attracted significant interest in applications for formulating carriers (microparticles, nanoparticles, hydrogels, and polymersomes) which can be prepared using the spontaneous phase separation of ATPSs as a driving force, and loaded with a wide range of bioactive materials, including small molecule drugs, proteins, and cells, for delivery applications. This review provides a detailed analysis of various ATPSs, including strategies employed for particle formation, polymerization of droplets in ATPSs, phase-guided block copolymer assemblies, and stimulus-responsive carriers. Processes for loading various bioactive payloads are discussed, and applications of these systems for drug delivery are summarized and discussed.
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  • 文章类型: Journal Article
    自身免疫,过敏,移植排斥是目前无法治愈的慢性疾病的集合,大大降低了患者的生活质量,消耗大量的医疗资源。这些疾病中的每一种的基础是免疫系统失调,其导致针对自身或无害抗原的炎症反应的增加。因此,患病患者需要坚持多种免疫调节药物的终身治疗方案,以控制疾病和恢复机构。不幸的是,目前的免疫调节药物与无数的副作用和不良事件有关,例如癌症风险增加和严重感染风险增加,这会对患者的依从率和生活质量产生负面影响。免疫工程领域是一门新学科,旨在利用内源性生物途径来阻止疾病并使用基于生物材料的新型策略将副作用降至最低。我们强调和讨论具有固有免疫调节特性的聚合物微米/纳米颗粒,目前正在研究基于生物材料的治疗自身免疫的治疗方法。过敏,和移植排斥。
    Autoimmunity, allergy, and transplant rejection are a collection of chronic diseases that are currently incurable, drastically decrease patient quality of life, and consume considerable health care resources. Underlying each of these diseases is a dysregulated immune system that results in the mounting of an inflammatory response against self or an innocuous antigen. As a consequence, afflicted patients are required to adhere to lifelong regimens of multiple immunomodulatory drugs to control disease and reclaim agency. Unfortunately, current immunomodulatory drugs are associated with a myriad of side effects and adverse events, such as increased risk of cancer and increased risk of serious infection, which negatively impacts patient adherence rates and quality of life. The field of immunoengineering is a new discipline that aims to harness endogenous biological pathways to thwart disease and minimize side effects using novel biomaterial-based strategies. We highlight and discuss polymeric micro/nanoparticles with inherent immunomodulatory properties that are currently under investigation in biomaterial-based therapies for treatment of autoimmunity, allergy, and transplant rejection.
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  • 文章类型: Journal Article
    结核病(TB)是由结核分枝杆菌(M.tb),2022年全球约有130万人死亡。使用抗结核药物的口服治疗通常不能在原发感染部位(肺)达到治疗浓度。在这项研究中,我们开发了氯法齐明(CFZ)干粉可吸入制剂(DPI),以提供局部给药并将全身不良反应降至最低.通过单乳液溶剂蒸发技术开发了含有CFZ的聚(乳酸-共-乙醇酸)(PLGA)微粒(MPs)。氯法齐明微粒(CFZMPs)的包封率和载药量为66.40±2.22%w/w和33.06±1.45µg/mg,分别。为了便于肺部给药,将MPs悬浮液喷雾干燥以产生干粉制剂(CFZSDMPs)。喷雾干燥对粒度(~1μm)没有影响,zeta电位(-31.42mV),和诱捕效率。CFZSDMPs研究的固态分析(PXRD和DSC)证明了药物在聚合物中的包封。药物释放研究显示药物持续释放。优化的配方表现出优异的雾化性能,提示在较深的肺部区域有效沉积。针对H37Ra的体外抗菌研究显示,与游离药物相比,喷雾干燥制剂的功效提高(八倍)。因此,氯法齐明干粉制剂具有治疗结核病的巨大潜力,其具有局部肺部递送和改善的患者依从性。
    Tuberculosis (TB) is an airborne bacterial infection caused by Mycobacterium tuberculosis (M. tb), resulting in approximately 1.3 million deaths in 2022 worldwide. Oral therapy with anti-TB drugs often fails to achieve therapeutic concentrations at the primary infection site (lungs). In this study, we developed a dry powder inhalable formulation (DPI) of clofazimine (CFZ) to provide localized drug delivery and minimize systemic adverse effects. Poly (lactic acid-co-glycolic acid) (PLGA) microparticles (MPs) containing CFZ were developed through a single emulsion solvent evaporation technique. Clofazimine microparticles (CFZ MPs) displayed entrapment efficiency and drug loading of 66.40 ± 2.22 %w/w and 33.06 ± 1.45 µg/mg, respectively. To facilitate pulmonary administration, MPs suspension was spray-dried to yield a dry powder formulation (CFZ SD MPs). Spray drying had no influence on particle size (~1 µm), zeta potential (-31.42 mV), and entrapment efficiency. Solid state analysis (PXRD and DSC) of CFZ SD MPs studies demonstrated encapsulation of the drug in the polymer. The drug release studies showed a sustained drug release. The optimized formulation exhibited excellent aerosolization properties, suggesting effective deposition in the deeper lung region. The in vitro antibacterial studies against H37Ra revealed improved (eight-fold) efficacy of spray-dried formulation in comparison to free drug. Hence, clofazimine dry powder formulation presents immense potential for the treatment of tuberculosis with localized pulmonary delivery and improved patient compliance.
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  • 文章类型: Journal Article
    这项研究的目的是研究物理化学,结构,和基于羧甲基纤维素(CMC)的冷冻凝胶珠的体外释放特性,其中包含用于结肠靶向递送系统的白藜芦醇负载的微粒(MP)。CMC基冷冻凝胶珠通过不同浓度的离子交联生产(2%,3%,4%)的AlCl3。基于FE-SEM图像,随着AlCl3浓度的增加,CMC基冷冻凝胶珠显示出更光滑的表面和更致密的内部结构,通过FT-IR分析证明这是由于CMC的-COO-基团与Al3之间的新交联。通过将AlCl3的浓度从2%提高到4%,冷冻凝胶珠的包封效率从79.48%显着提高到85.74%,分别。体外释放研究表明,在模拟胃条件下,所有基于CMC的冷冻凝胶珠对白藜芦醇的稳定性均高于MP,并且可以有效地将白藜芦醇递送至结肠而不会过早释放。
    The objective of this study was to investigate the physicochemical, structural, and in vitro release properties of carboxymethyl cellulose (CMC)-based cryogel beads incorporating resveratrol-loaded microparticles (MP) for colon-targeted delivery system. CMC-based cryogel beads were produced by ionic cross-linking with different concentrations (2%, 3%, and 4%) of AlCl3. Based on FE-SEM images, CMC-based cryogel beads showed a smoother surface and more compact internal structure with increasing AlCl3 concentrations, which was proven to be due to the new cross-linking between the -COO- group of CMC and Al3+ by FT-IR analysis. The encapsulation efficiency of the cryogel beads was significantly increased from 79.48% to 85.74% by elevating the concentrations of AlCl3 from 2% to 4%, respectively. In vitro release study showed that all CMC-based cryogel beads had higher stability for resveratrol than MP in simulated gastric conditions and can efficiently deliver resveratrol to colon without the premature release.
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  • 文章类型: Journal Article
    引导骨再生(GBR)是一种广泛使用的方法,可防止软组织快速生长成骨缺损。在不同类型的膜中,使用胶原蛋白膜是金标准。然而,这些膜植入在组织位置,在那里会发生严重的急性炎症,并可能受到负面影响。这项研究的目的是开发一种用于GBR的胶原基膜,该膜掺入了藻酸盐-羟基磷灰石微粒。使用I型胶原和明胶以及藻酸盐-羟基磷灰石微粒制造膜。通过扫描电子显微镜和共聚焦显微镜评估膜的形貌;在盐水中过夜孵育后溶胀的稳定性以及通过拉伸测试对胶原酶的酶降解和机械性能。此外,用SaOs-2细胞和THP-1巨噬细胞评估生物学反应,以确定碱性磷酸酶活性和炎性细胞因子释放.我们的结果表明,掺入不同百分比的这些微粒可以引起表面形貌的变化。当分析生物反应时,膜对THP-1巨噬细胞或SaOs-2细胞均无细胞毒性,且不诱导促炎细胞因子的释放.然而,不同的表面形貌并没有诱导巨噬细胞形态的变化和促炎和抗炎细胞因子的释放,这表明表面粗糙度对巨噬细胞行为的影响可能取决于其他因素,如基质硬度和成分。带有包埋的藻酸盐-羟基磷灰石微粒的胶原-明胶膜增加了ALP活性,表明它们对骨骼再生有积极的影响,保持不影响促炎和抗炎细胞因子的释放。
    Guided bone regeneration (GBR) is a widely used procedure that prevents the fast in-growth of soft tissues into bone defect. Among the different types of membranes, the use of collagen membranes is the gold standard. However, these membranes are implanted in tissue location where a severe acute inflammation will occur and can be negatively affected. The aim of this study was to develop a collagen-based membrane for GBR that incorporated alginate-hydroxyapatite microparticles. Membranes were manufactured using collagen type I and gelatin and alginate-hydroxyapatite microparticles. Membranes were assessed in terms of topography by scanning electron microscopy and confocal microscopy; stability by swelling after an overnight incubation in saline and enzymatic degradation against collagenase and mechanical properties by tensile tests. Furthermore, the biological response was assessed with SaOs-2 cells and THP-1 macrophages to determine alkaline phosphatase activity and inflammatory cytokine release. Our results showed that the incorporation of different percentages of these microparticles could induce changes in the surface topography. When the biological response was analyzed, either membranes were not cytotoxic to THP-1 macrophages or to SaOs-2 cells and they did not induce the release of pro-inflammatory cytokines. However, the different surface topographies did not induce changes in the macrophage morphology and the release of pro- and anti-inflammatory cytokines, suggesting that the effect of surface roughness on macrophage behavior could be dependent on other factors such as substrate stiffness and composition. Collagen-gelatin membranes with embedded alginate-hydroxyapatite microparticles increased ALP activity, suggesting a positive effect of them on bone regeneration, remaining unaffected the release of pro- and anti-inflammatory cytokines.
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  • 文章类型: Journal Article
    已知顺铂会导致内耳功能障碍。越来越多的证据表明,顺铂诱导的螺旋或Scarpa神经节神经元脱髓鞘可能在药物诱导的耳毒性以及传入神经元损伤中起额外作用。雪旺氏细胞产生髓鞘,可能有机会通过促进雪旺氏细胞活力来减少耳毒性内耳损伤。这项工作描述了顺铂诱导的雪旺氏细胞损伤的细胞模型,并研究了抗氧化剂N-乙酰半胱氨酸促进雪旺氏细胞活力的能力。然后制造药物洗脱微粒的局部递送系统,characterized,并调查了生物活性。
    RSC96大鼠施旺细胞给予不同浓度的顺铂以获得剂量曲线并鉴定50%细胞的致死浓度(LC50)。在随后的实验中,RSC96细胞用顺铂和重悬或洗脱的N-乙酰半胱氨酸共同处理。用CCK8测定评估细胞活力。
    顺铂的LC50剂量测定为3.76μM(p=2.2×10-16)。当与顺铂和治疗浓度的重悬或洗脱的N-乙酰半胱氨酸共同给药时,与单独给予顺铂的细胞相比,施万细胞具有增加的活力。
    在该体外模型中表征了顺铂损伤后的RSC96Schwann细胞损伤。顺铂在生理浓度下引起损伤,N-乙酰半胱氨酸改善了细胞活力并减轻了这种损伤。将N-乙酰半胱氨酸包装到微粒中,洗脱的N-乙酰半胱氨酸保留其增加细胞活力的能力,因此证明有希望作为一种治疗来抵消顺铂诱导的耳毒性。
    N/A喉镜,2023年。
    UNASSIGNED: Cisplatin is known to cause inner ear dysfunction. There is growing evidence that cisplatin-induced demyelination of spiral or Scarpa\'s ganglion neurons may play an additional role in drug-induced ototoxicity alongside afferent neuron injury. As Schwann cells produce myelin, there may be an opportunity to reduce ototoxic inner ear damage by promoting Schwann cell viability. This work describes a cellular model of cisplatin-induced Schwann cell injury and investigates the ability of the antioxidant N-acetylcysteine to promote Schwann cell viability. A local delivery system of drug-eluting microparticles was then fabricated, characterized, and investigated for bioactivity.
    UNASSIGNED: RSC96 rat Schwann cells were dosed with varying concentrations of cisplatin to obtain a dose curve and identify the lethal concentration of 50% of the cells (LC50). In subsequent experiments, RSC96 cells were co-treated with cisplatin and both resuspended or eluted N-acetylcysteine. Cell viability was assessed with the CCK8 assay.
    UNASSIGNED: The LC50 dose of cisplatin was determined to be 3.76 μM (p = 2.2 x 10-16). When co-dosed with cisplatin and a therapeutic concentration of resuspended or eluted N-acetylcysteine, Schwann cells had an increased viability compared to cells dosed with cisplatin alone.
    UNASSIGNED: RSC96 Schwann cell injury following cisplatin insult is characterized in this in vitro model. Cisplatin caused injury at physiologic concentrations and N-acetylcysteine improved cell viability and mitigated this injury. N-acetylcysteine was packaged into microparticles and eluted N-acetylcysteine retained its ability to increase cell viability, thus demonstrating promise as a therapeutic to offset cisplatin-induced ototoxicity.
    UNASSIGNED: N/A Laryngoscope, 2023.
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  • 文章类型: Journal Article
    免疫原性细胞死亡(ICD)在触发肿瘤微环境(TME)中的抗肿瘤免疫反应中起着至关重要的作用。最近,相当多的注意力一直集中在铁性上,一种由细胞内铁诱导的ICD,已被证明可改变TME的免疫沙漠状态。然而,在以免疫沙漠为特征的癌症中,比如前列腺癌,诱导高水平铁中毒的策略仍然有限。辐射肿瘤细胞衍生微粒(RMPs)是放疗模拟物,已被证明可以激活cGAS-STING通路,诱导肿瘤细胞铁性凋亡,抑制M2巨噬细胞极化。RMP还可以充当具有生物相容性的试剂的载体。在本研究中,我们设计了一种治疗系统,其中将铁凋亡诱导物RSL-3加载到RMPs中,在使用RM-1细胞建立的体外和体内前列腺癌模型中进行了测试。凋亡诱导剂CT20肽(CT20p)也被添加到RMPs中以加重铁凋亡。我们的结果表明,RSL-3-和CT20p负载的RMPs(RC@RMPs)导致RM-1细胞的铁凋亡和凋亡。此外,CT20p通过促进活性氧(ROS)的产生对铁凋亡具有协同作用,脂质过氧化氢生产,和线粒体不稳定。RC@RMPs升高的树突状细胞(DC)表达MHCII,CD80和CD86促进M1巨噬细胞极化。在小鼠皮下移植的RM-1肿瘤模型中,RC@RMPs通过DC激活抑制肿瘤生长并延长生存时间,巨噬细胞重编程,增强CD8+T细胞浸润,和肿瘤中促炎细胞因子的产生。此外,抗PD-1联合治疗可改善RM-1肿瘤抑制。这项研究为前列腺癌免疫疗法的铁凋亡的协同增强提供了策略。
    Immunogenic cell death (ICD) plays a crucial role in triggering the antitumor immune response in the tumor microenvironment (TME). Recently, considerable attention has been dedicated to ferroptosis, a type of ICD that is induced by intracellular iron and has been demonstrated to change the immune desert status of the TME. However, among cancers that are characterized by an immune desert, such as prostate cancer, strategies for inducing high levels of ferroptosis remain limited. Radiated tumor cell-derived microparticles (RMPs) are radiotherapy mimetics that have been shown to activate the cGAS-STING pathway, induce tumor cell ferroptosis, and inhibit M2 macrophage polarization. RMPs can also act as carriers of agents with biocompatibility. In the present study, we designed a therapeutic system wherein the ferroptosis inducer RSL-3 was loaded into RMPs, which were tested in in vitro and in vivo prostate carcinoma models established using RM-1 cells. The apoptosis inducer CT20 peptide (CT20p) was also added to the RMPs to aggravate ferroptosis. Our results showed that RSL-3- and CT20p-loaded RMPs (RC@RMPs) led to ferroptosis and apoptosis of RM-1 cells. Moreover, CT20p had a synergistic effect on ferroptosis by promoting reactive oxygen species (ROS) production, lipid hydroperoxide production, and mitochondrial instability. RC@RMPs elevated dendritic cell (DC) expression of MHCII, CD80, and CD86 and facilitated M1 macrophage polarization. In a subcutaneously transplanted RM-1 tumor model in mice, RC@RMPs inhibited tumor growth and prolonged survival time via DC activation, macrophage reprogramming, enhancement of CD8+ T cell infiltration, and proinflammatory cytokine production in the tumor. Moreover, combination treatment with anti-PD-1 improved RM-1 tumor inhibition. This study provides a strategy for the synergistic enhancement of ferroptosis for prostate cancer immunotherapies.
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  • 文章类型: Journal Article
    非感染性葡萄膜炎是视力损害的主要原因,皮质类固醇药物治疗是导致严重副作用的主要临床策略。雷帕霉素(RAPA),一种有效的免疫调节剂,是非感染性葡萄膜炎的有希望的治疗方法。然而,因为需要高剂量和频繁剂量,由于其严重的毒性,将其临床转化为非感染性葡萄膜炎治疗是一个巨大的挑战。在本研究中,我们设计了一种基于可生物降解嵌段聚合物的可注射微粒药物递送系统(即,聚己内酯-聚(乙二醇)-聚己内酯,PCEC)通过结膜下注射途径有效地眼部递送RAPA,并在实验性自身免疫性葡萄膜炎(EAU)大鼠模型中研究了其治疗功效。使用乳液蒸发法制备RAPA-PCEC微粒,并使用扫描电子显微镜彻底表征,傅里叶变换红外光谱,X射线衍射,和差示扫描量热法。形成的微粒在28天内表现出缓慢的体外降解,并在4周内提供了RAPA的体外和体内缓释。此外,一次结膜下注射PCEC微粒可产生较高的眼部耐受性.更重要的是,结膜下注射RAPA-PCEC微粒通过减少炎性细胞浸润,以剂量依赖性方式显着减弱了EAU的临床体征(即,CD45+细胞和Th17细胞)并抑制小胶质细胞活化。总的来说,这些可注射微粒系统可能是用于眼内递送RAPA治疗非感染性葡萄膜炎的有前景的载体.
    Noninfective uveitis is a major cause of vision impairment, and corticosteroid medication is a mainstay clinical strategy that causes severe side effects. Rapamycin (RAPA), a potent immunomodulator, is a promising treatment for noninfective uveitis. However, because high and frequent dosages are required, it is a great challenge to implement its clinical translation for noninfective uveitis therapy owing to its serious toxicity. In the present study, we engineered an injectable microparticulate drug delivery system based on biodegradable block polymers (i.e., polycaprolactone-poly (ethylene glycol)-polycaprolactone, PCEC) for efficient ocular delivery of RAPA via a subconjunctival injection route and investigated its therapeutic efficacy in an experimental autoimmune uveitis (EAU) rat model. RAPA-PCEC microparticles were fabricated using the emulsion-evaporation method and thoroughly characterized using scanning electron microscopy, fourier transform infrared spectroscopy, X-ray diffraction, and differential scanning calorimetry. The formed microparticles exhibited slow in vitro degradation over 28 days, and provided both in vitro and in vivo sustained release of RAPA over 4 weeks. Additionally, a single subconjunctival injection of PCEC microparticles resulted in high ocular tolerance. More importantly, subconjunctival injection of RAPA-PCEC microparticles significantly attenuated the clinical signs of EAU in a dose-dependent manner by reducing inflammatory cell infiltration (i.e., CD45+ cells and Th17 cells) and inhibiting microglial activation. Overall, this injectable microparticulate system may be promising vehicle for intraocular delivery of RAPA for the treatment of noninfective uveitis.
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