delivery systems

输送系统
  • 文章类型: Journal Article
    输送系统对于先天性心脏病患者植入医疗器械至关重要。然而,很少有数据可以比较各种递送系统的优缺点。
    本文介绍了用于输送房间隔封堵器装置的输送系统和方法,室间隔封堵器,闭塞动脉导管的装置,和经导管肺动脉瓣。比较了与准备和装载有关的输送系统,输送鞘/导管的定位,部署,重新捕获和重新定位的能力,以及设备释放。
    对于大多数ASD/VSD/PDA封堵器,在过去的20年中,基本的交付机制几乎没有变化。未来的修改可以集中于对线缆系统的有意义的修改,其降低刚度并改善与设备的连接处的角度。在接下来的5-10年里,预计将看到用于经导管肺动脉瓣植入术的输送系统发生重大变化,这导致在部署过程中重新捕获和重新定位自膨式经导管瓣膜的能力得到改善,结合抗扭结鞘,便于在通常复杂的右心室流出道上轻松追踪。
    UNASSIGNED: Delivery systems are crucially important for the implantation of medical devices in patients with congenital heart disease. However, very little data is available comparing the advantages and disadvantages of the various delivery systems.
    UNASSIGNED: This article describes the delivery systems and methods used for delivery of atrial septal occluder devices, ventricular septal occluder devices, devices to occlude patent arterial ducts, and transcatheter pulmonary valves. Delivery systems are compared relating to prepping and loading, positioning of the delivery sheath/catheter, deployment, ability to recapture and reposition, as well as device release.
    UNASSIGNED: For most ASD/VSD/PDA occluder devices, the basic delivery mechanism has changed very little over the preceding 20 years. Future modifications may focus on meaningful modifications to the cable systems that reduce stiffness and improve angulation at the connection to the device. Over the next 5-10 years, it is expected to see significant changes to delivery systems used for transcatheter pulmonary valve implantation, that result in improvements in the ability to recapture and reposition self-expandable transcatheter valves during the deployment process, combined with kink resistant sheaths that facilitate easy tracking across often complex right ventricular outflow tracts.
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  • 文章类型: Journal Article
    体内不同部位的微生物群与疾病密切相关。益生菌的摄入是缓解疾病和辅助治疗的有效策略。然而,益生菌可能遭受恶劣的环境和定殖抗性,使得难以维持足够数量的活益生菌以到达目标部位并发挥其原始益生菌作用。益生菌的封装是一种有效的策略。因此,益生菌递送系统,作为有效的方法,不断开发和创新,以确保益生菌有效地输送到目标部位。在这次审查中,最初,从四个方面综述了益生菌递送系统的设计:益生菌的特性,加工技术,细胞来源的壁材料,以及墙体材料之间的相互作用。随后,该综述侧重于针对四个主要微生物定植位点的益生菌递送系统的效果:口腔,皮肤,肠,还有阴道,以及肿瘤等疾病部位。最后,这篇综述还讨论了益生菌递送系统在疾病治疗中的安全性问题,以及在临床研究中实施该方法的挑战和局限性。有必要进行更多的临床研究,以评估不同益生菌递送系统在疾病治疗中的有效性。
    The microbiota at different sites in the body is closely related to disease. The intake of probiotics is an effective strategy to alleviate diseases and be adjuvant in their treatment. However, probiotics may suffer from harsh environments and colonization resistance, making it difficult to maintain a sufficient number of live probiotics to reach the target sites and exert their original probiotic effects. Encapsulation of probiotics is an effective strategy. Therefore, probiotic delivery systems, as effective methods, have been continuously developed and innovated to ensure that probiotics are effectively delivered to the targeted site. In this review, initially, the design of probiotic delivery systems is reviewed from four aspects: probiotic characteristics, processing technologies, cell-derived wall materials, and interactions between wall materials. Subsequently, the review focuses on the effects of probiotic delivery systems that target four main microbial colonization sites: the oral cavity, skin, intestine, and vagina, as well as disease sites such as tumors. Finally, this review also discusses the safety concerns of probiotic delivery systems in the treatment of disease and the challenges and limitations of implementing this method in clinical studies. It is necessary to conduct more clinical studies to evaluate the effectiveness of different probiotic delivery systems in the treatment of diseases.
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  • 文章类型: Journal Article
    基因治疗和基因编辑技术的最新进展为成功治疗神经系统疾病提供了非常实际的潜力。然而,由于其解剖复杂性和许多分子不渗透的高度限制性微脉管系统,药物递送限制继续阻碍靶向大脑的可行治疗干预。实现基于基因的疗法的治疗潜力需要强大的封装和安全有效的递送到靶细胞。尽管病毒载体已广泛用于靶向递送基于基因的疗法,缺点,如宿主基因组整合,延长表达,不希望的脱靶突变,和免疫原性导致了替代策略的发展。工程化病毒样颗粒(eVLP)是一种新兴的,有希望的平台,可以通过假型化实现神经营养。这篇综述概述了改善eVLP神经嗜性的策略,用于治疗性脑递送基因编辑剂。
    Recent advances in gene therapy and gene-editing techniques offer the very real potential for successful treatment of neurological diseases. However, drug delivery constraints continue to impede viable therapeutic interventions targeting the brain due to its anatomical complexity and highly restrictive microvasculature that is impervious to many molecules. Realizing the therapeutic potential of gene-based therapies requires robust encapsulation and safe and efficient delivery to the target cells. Although viral vectors have been widely used for targeted delivery of gene-based therapies, drawbacks such as host genome integration, prolonged expression, undesired off-target mutations, and immunogenicity have led to the development of alternative strategies. Engineered virus-like particles (eVLPs) are an emerging, promising platform that can be engineered to achieve neurotropism through pseudotyping. This review outlines strategies to improve eVLP neurotropism for therapeutic brain delivery of gene-editing agents.
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  • 文章类型: Journal Article
    随着肿瘤免疫治疗技术的不断进步,研究人员正在积极探索新的治疗方法。肽治疗性癌症疫苗因其在改善患者预后方面的潜力而引起了极大的关注。尽管有潜力,只有一种基于肽的癌症疫苗获得了美国食品和药物管理局(FDA)的批准.全面了解潜在的机制和当前的发展状况对于推进这些疫苗至关重要。本文对基于肽的癌症疫苗的生产原理和治疗机制进行了深入分析,突出了常用的基于肽的癌症疫苗,并研究了将这些疫苗与免疫疗法相结合的协同作用,靶向治疗,放射治疗,和化疗。虽然一些研究取得了次优结果,联合治疗的潜力仍然很大.此外,我们讨论了与基于肽的癌症疫苗相关的管理和不良事件,注意到与传统的放疗和化疗相比,它们的安全性相对较高。最后,我们还讨论了佐剂和靶向递送系统在增强疫苗效力中的作用。总之,这篇综述全面概述了基于肽的癌症疫苗接种的现状,并强调了其作为关键免疫疗法的潜力。
    With the continuous advancements in tumor immunotherapy, researchers are actively exploring new treatment methods. Peptide therapeutic cancer vaccines have garnered significant attention for their potential in improving patient outcomes. Despite its potential, only a single peptide-based cancer vaccine has been approved by the U.S. Food and Drug Administration (FDA). A comprehensive understanding of the underlying mechanisms and current development status is crucial for advancing these vaccines. This review provides an in-depth analysis of the production principles and therapeutic mechanisms of peptide-based cancer vaccines, highlights the commonly used peptide-based cancer vaccines, and examines the synergistic effects of combining these vaccines with immunotherapy, targeted therapy, radiotherapy, and chemotherapy. While some studies have yielded suboptimal results, the potential of combination therapies remains substantial. Additionally, we addressed the management and adverse events associated with peptide-based cancer vaccines, noting their relatively higher safety profile compared to traditional radiotherapy and chemotherapy. Lastly, we also discussed the roles of adjuvants and targeted delivery systems in enhancing vaccine efficacy. In conclusion, this review comprehensively outlines the current landscape of peptide-based cancer vaccination and underscores its potential as a pivotal immunotherapy approach.
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  • 文章类型: Journal Article
    基于mRNA的疫苗象征着个性化医学治疗感染性和非感染性疾病的新范式转变。然而,与目前批准的制剂相关的反应原性限制了它们在自身炎症性疾病中的适用性,如肿瘤治疗。在这项研究中,我们提出了一个递送系统,显示出受控的免疫原性和最小的非特异性炎症,允许将mRNA选择性递送至淋巴结髓质区域内的抗原呈递细胞(APC)。我们的平台通过优化隐身和靶向特性,提供对淋巴结内纳米颗粒运输的精确控制,以及随后的调理过程。通过靶向特定的细胞,我们观察到强大的适应性和体液免疫反应,它有望用于预防和治疗抗肿瘤疫苗。通过纳米粒子分布的空间规划,我们可以促进强有力的免疫接种,从而提高和扩大mRNA疫苗的利用率。这种创新方法标志着靶向纳米医学领域的显著进步。
    mRNA-based vaccines symbolize a new paradigm shift in personalized medicine for the treatment of infectious and non-infectious diseases. However, the reactogenicity associated with the currently approved formulations limits their applicability in autoinflammatory disorders, such as tumour therapeutics. In this study, we present a delivery system showing controlled immunogenicity and minimal non-specific inflammation, allowing for selective delivery of mRNA to antigen presenting cells (APCs) within the medullary region of the lymph nodes. Our platform offers precise control over the trafficking of nanoparticles within the lymph nodes by optimizing stealth and targeting properties, as well as the subsequent opsonization process. By targeting specific cells, we observed a potent adaptive and humoral immune response, which holds promise for preventive and therapeutic anti-tumoral vaccines. Through spatial programming of nanoparticle distribution, we can promote robust immunization, thus improving and expanding the utilization of mRNA vaccines. This innovative approach signifies a remarkable step forward in the field of targeted nanomedicine.
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  • 文章类型: Journal Article
    以益生菌为基础的功能性食品或药物由于益生菌与人类健康的关系日益明确而获得了前所未有的关注和发展。益生菌可以调节肠道菌群,动态参与各种生理活动直接影响人体健康。一些基于益生菌的功能制剂在治疗多种难治性疾病方面显示出巨大的潜力。目前,益生菌细胞在体外和体内复杂环境中的存活和活性已被优先考虑,和基于食品衍生材料的各种封装系统已经被设计和构造以保护和递送益生菌。然而,传统的封装技术无法实现对单一益生菌的精确保护,这使得它在发布后无法产生显著的效果。在这种情况下,单细胞封装系统可以基于生物接口组装,以保护和功能化单个益生菌细胞,最大化他们的生理活动。本文综述了益生菌在食品加工中面临的艰巨挑战,storage,人类消化,和常用的益生菌封装系统。此外,介绍了一种基于单细胞涂层的益生菌封装新技术,即,\"盔甲益生菌\"。我们专注于分类,结构设计,和装甲涂层的功能特性,并强调了装甲益生菌在人体健康调节中的基本功能特征,包括调节肠道健康和有针对性的生物成像和治疗病变组织。随后,的好处,局限性,潜在的挑战,并提出了装甲益生菌的未来发展方向。我们希望这篇综述可以为开发单细胞益生菌封装系统提供新的见解和思路。
    Functional foods or drugs based on probiotics have gained unprecedented attention and development due to the increasingly clear relationship between probiotics and human health. Probiotics can regulate intestinal microbiota, dynamically participating in various physiological activities to directly affect human health. Some probiotic-based functional preparations have shown great potential in treating multiple refractory diseases. Currently, the survival and activity of probiotic cells in complex environments in vitro and in vivo have taken priority, and various encapsulation systems based on food-derived materials have been designed and constructed to protect and deliver probiotics. However, traditional encapsulation technology cannot achieve precise protection for a single probiotic, which makes it unable to have a significant effect after release. In this case, single-cell encapsulation systems can be assembled based on biological interfaces to protect and functionalize individual probiotic cells, maximizing their physiological activity. This review discussed the arduous challenges of probiotics in food processing, storage, human digestion, and the commonly used probiotic encapsulation system. Besides, a novel technology of probiotic encapsulation was introduced based on single-cell coating, namely, \"armor probiotics\". We focused on the classification, structural design, and functional characteristics of armor coatings, and emphasized the essential functional characteristics of armor probiotics in human health regulation, including regulating intestinal health and targeted bioimaging and treatment of diseased tissues. Subsequently, the benefits, limitations, potential challenges, as well as future direction of armor probiotics were put forward. We hope this review may provide new insights and ideas for developing a single-cell probiotics encapsulating system.
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  • 文章类型: Journal Article
    本研究旨在研究界面层组成和结构对形成的影响,Pickering乳液的理化性质和稳定性。使用豌豆蛋白分离物(PPI)形成界面层,PPI微凝胶颗粒(PPIMP),PPIMP和海藻酸钠(PPIMP-SA)的混合物,或PPIMP-SA缀合物。然后在这些Pickering乳液中评估对不同疏水性生物活性物质的包封和保护作用。结果表明,PPIMP-SA结合物在油滴表面周围形成了厚而坚固的界面层,这增加了乳液对聚结的抵抗力,乳化液,和环境压力,包括加热,曝光,和冻融循环。此外,通过PPIMP-SA缀合物稳定的乳液显着提高了疏水性生物活性物质的光热稳定性,与非封装形式相比,保留了较高百分比的原始含量。总的来说,本研究开发的新型蛋白质微凝胶和缀合物具有提高乳化食品理化稳定性的巨大潜力。
    This study aims to investigate the effects of interfacial layer composition and structure on the formation, physicochemical properties and stability of Pickering emulsions. Interfacial layers were formed using pea protein isolate (PPI), PPI microgel particles (PPIMP), a mixture of PPIMP and sodium alginate (PPIMP-SA), or PPIMP-SA conjugate. The encapsulation and protective effects on different hydrophobic bioactives were then evaluated within these Pickering emulsions. The results demonstrated that the PPIMP-SA conjugate formed thick and robust interfacial layers around the oil droplet surfaces, which increased the resistance of the emulsion to coalescence, creaming, and environmental stresses, including heating, light exposure, and freezing-thawing cycle. Additionally, the emulsion stabilized by the PPIMP-SA conjugate significantly improved the photothermal stability of hydrophobic bioactives, retaining a higher percentage of their original content compared to those in non-encapsulated forms. Overall, the novel protein microgels and the conjugate developed in this study have great potential for improving the physicochemical stability of emulsified foods.
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  • 文章类型: Journal Article
    细胞外囊泡(EV)在伤口愈合中的利用已得到充分证明。然而,通过在伤口部位皮下注射直接施用游离EV可能导致生物活性成分的快速消散和治疗功效降低.功能化水凝胶提供有效的保护,以及确保伤口愈合过程中电动汽车的持续释放和生物活性,使它们成为交付电动汽车的理想候选材料。在这次审查中,我们介绍了电动汽车加速伤口愈合的机制,然后详细阐述工程电动汽车的建设策略。随后,我们讨论了水凝胶作为缓释系统的合成策略和应用,以促进复杂的伤口愈合。此外,面对复杂的伤口,具有特定伤口微环境调节能力的功能化水凝胶,如抗菌剂,抗炎,和免疫调节,用于加载工程电动汽车,提供解决这些治疗挑战的潜在方法。最终,我们仔细研究潜在的未来轨迹和前景,为生物医学应用的人工智能(AI)赋能材料和3D生物打印多功能基于水凝胶的工程电动汽车输送敷料的发展提供了新的观点。
    The utilization of extracellular vesicles (EVs) in wound healing has been well-documented. However, the direct administration of free EVs via subcutaneous injection at wound sites may result in the rapid dissipation of bioactive components and diminished therapeutic efficacy. Functionalized hydrogels provide effective protection, as well as ensure the sustained release and bioactivity of EVs during the wound healing process, making them an ideal candidate material for delivering EVs. In this review, we introduce the mechanisms by which EVs accelerate wound healing, and then elaborate on the construction strategies for engineered EVs. Subsequently, we discuss the synthesis strategies and application of hydrogels as delivery systems for the sustained release of EVs to enhance complicated wound healing. Furthermore, in the face of complicated wounds, functionalized hydrogels with specific wound microenvironment regulation capabilities, such as antimicrobial, anti-inflammatory, and immune regulation, used for loading engineered EVs, provide potential approaches to addressing these healing challenges. Ultimately, we deliberate on potential future trajectories and outlooks, offering a fresh viewpoint on the advancement of artificial intelligence (AI)-energized materials and 3D bio-printed multifunctional hydrogel-based engineered EVs delivery dressings for biomedical applications.
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  • 文章类型: Journal Article
    RNA药物代表了治疗和预防具有全球意义的重大疾病的范式转变。例如,传染病。针对严重急性呼吸道综合症冠状病毒2(SARS-CoV-2)的非常成功的信使RNA(mRNA)疫苗在2019年冠状病毒大流行期间以创纪录的速度开发。其结果是疫苗开发时间大大缩短,结合适应性使RNA疫苗技术对传染病和大流行防备极具吸引力。这里,我们回顾了基于不同RNA模式的传染病RNA疫苗的设计和交付的最新技术,包括线性mRNA,自扩增RNA,反式扩增RNA,和环状RNA。我们概述了用于传染病的RNA疫苗的临床管道,并提出分析程序,这对于表征质量属性和保证其质量至关重要,我们讨论了使用RNA疫苗对抗SARS-CoV-2以外的病原体的未来前景。
    RNA medicines represent a paradigm shift in treatment and prevention of critical diseases of global significance, e.g., infectious diseases. The highly successful messenger RNA (mRNA) vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were developed at record speed during the coronavirus disease 2019 pandemic. A consequence of this is exceptionally shortened vaccine development times, which in combination with adaptability makes the RNA vaccine technology highly attractive against infectious diseases and for pandemic preparedness. Here, we review state of the art in the design and delivery of RNA vaccines for infectious diseases based on different RNA modalities, including linear mRNA, self-amplifying RNA, trans-amplifying RNA, and circular RNA. We provide an overview of the clinical pipeline of RNA vaccines for infectious diseases, and present analytical procedures, which are paramount for characterizing quality attributes and guaranteeing their quality, and we discuss future perspectives for using RNA vaccines to combat pathogens beyond SARS-CoV-2.
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  • 文章类型: Journal Article
    聚-γ-谷氨酸(γ-PGA)是一种富含羧酸,生物衍生,水溶性,可食用,补水,由几种微生物天然产生的非免疫原性聚合物。这里,我们再次强调了纳豆芽孢杆菌在整个海藻上自然产生γ-PGA的能力,以及受Mn(2)的存在影响的材料的产率和化学性质。透明质酸(HA)是一种胞外糖胺聚糖,具有高浓度的羧酸和羟基,是实现众多应用的关键。目前,有很强的环境(溶剂使用),社会(非素食提取),和经济因素推动这种材料通过原核微生物的生物合成,尚不可扩展或可持续。我们的研究旨在研究一种创新的原材料,它可以将卓越的吸湿性和紫外线防护结合到化妆品行业。观察到市售γ-PGA与常规保湿剂(HA和甘油)的水合作用相当;然而,从海藻衍生的γ-PGA观察到更大的水合能力。随此,成功掺入了海藻衍生的γ-PGA(0.2-2w/v%),对于几个模型乳膏系统,在300和400nm处报告了吸光度。随着粘度的降低,所有基于γ-PGA的乳膏都显示出剪切稀化行为,随着剪切速率的增加。尽管在面霜中使用商业γ-PGA并没有表明对流变行为有显著影响,这被证实是相似分子量的结果。通过体外MTT分析,海藻衍生的γ-PGA乳膏系统对HaCaT角质形成细胞模型没有任何负面影响。
    Poly-γ-glutamic acid (γ-PGA) is a carboxylic-acid-rich, bio-derived, water-soluble, edible, hydrating, non-immunogenic polymer produced naturally by several microorganisms. Here, we re-emphasise the ability of Bacillus subtilis natto to naturally produce γ-PGA on whole seaweed, as well as for the yields and chemical properties of the material to be affected by the presence of Mn(2+). Hyaluronic acid (HA) is an extracellular glycosaminoglycan which presents a high concentration of carboxylic acid and hydroxyl groups, being key in fulfilling numerous applications. Currently, there are strong environmental (solvent use), social (non-vegan extraction), and economic factors pushing for the biosynthesis of this material through prokaryotic microorganisms, which is not yet scalable or sustainable. Our study aimed to investigate an innovative raw material which can combine both superior hygroscopicity and UV protection to the cosmetic industry. Comparable hydration effect of commercially available γ-PGA to conventional moisturising agents (HA and glycerol) was observed; however, greater hydration capacity was observed from seaweed-derived γ-PGA. Herewith, successful incorporation of seaweed-derived γ-PGA (0.2-2 w/v%) was achieved for several model cream systems with absorbances reported at 300 and 400 nm. All γ-PGA-based creams displayed shear thinning behaviour as the viscosity decreased, following increasing shear rates. Although the use of commercial γ-PGA within creams did not suggest a significant effect in rheological behaviour, this was confirmed to be a result of the similar molecular weight. Seaweed-derived γ-PGA cream systems did not display any negative effect on model HaCaT keratinocytes by means of in vitro MTT analysis.
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