Drug delivery system

药物递送系统
  • 文章类型: Journal Article
    缺血性脑卒中是一种涉及多个复杂生理过程的严重神经系统疾病,包括血管阻塞,脑组织缺血,能量代谢受损,细胞死亡,离子泵功能受损,和炎症反应。近年来,细胞膜功能化仿生纳米粒子作为一种新的治疗方法引起了人们的极大兴趣.这篇综述全面探讨了使用这些纳米颗粒治疗急性缺血性中风的机制和重要性,特别强调了它们通过细胞膜积极靶向治疗的潜力。我们概述了缺血性卒中的病理生理学,并介绍了仿生纳米粒子的研究进展。强调它们在药物输送和精准靶向治疗方面的潜力。本文重点研究了包裹在仿生细胞膜中的生物纳米颗粒,以靶向缺血性中风治疗。它强调了不同类型的细胞膜功能化的双离子纳米粒子,如红细胞的作用机制和研究进展,中性粒细胞,血小板,外泌体,巨噬细胞,神经干细胞治疗缺血性卒中,同时强调其改善脑组织缺血状态和减轻神经损伤和功能障碍的潜力。通过深入探索细胞膜功能化仿生纳米粒子在改善脑组织缺血状态同时减少神经损伤和功能障碍的潜在益处,本研究还提供了对神经干细胞的潜能以及细胞膜功能化仿生纳米粒子改善神经损伤和功能障碍的综合研究。然而,不可否认,在生物相容性方面仍然存在一些挑战和局限性,安全,和临床翻译的实际应用。
    Ischemic stroke is a serious neurological disease involving multiple complex physiological processes, including vascular obstruction, brain tissue ischemia, impaired energy metabolism, cell death, impaired ion pump function, and inflammatory response. In recent years, there has been significant interest in cell membrane-functionalized biomimetic nanoparticles as a novel therapeutic approach. This review comprehensively explores the mechanisms and importance of using these nanoparticles to treat acute ischemic stroke with a special emphasis on their potential for actively targeting therapies through cell membranes. We provide an overview of the pathophysiology of ischemic stroke and present advances in the study of biomimetic nanoparticles, emphasizing their potential for drug delivery and precision-targeted therapy. This paper focuses on bio-nanoparticles encapsulated in bionic cell membranes to target ischemic stroke treatment. It highlights the mechanism of action and research progress regarding different types of cell membrane-functionalized bi-onic nanoparticles such as erythrocytes, neutrophils, platelets, exosomes, macrophages, and neural stem cells in treating ischemic stroke while emphasizing their potential to improve brain tissue\'s ischemic state and attenuate neurological damage and dysfunction. Through an in-depth exploration of the potential benefits provided by cell membrane-functionalized biomimetic nanoparticles to improve brain tissue\'s ischemic state while reducing neurological injury and dysfunction, this study also provides comprehensive research on neural stem cells\' potential along with that of cell membrane-functionalized biomimetic nanoparticles to ameliorate neurological injury and dysfunction. However, it is undeniable that there are still some challenges and limitations in terms of biocompatibility, safety, and practical applications for clinical translation.
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  • 文章类型: Journal Article
    抑郁症是一种慢性精神障碍,其特征是持续的情绪低落和失去兴趣。抑郁症的治疗方法多种多样,但可能不足以治愈。基于药物的治疗方案具有诸如起效缓慢的缺点,低生物利用度,和药物副作用。纳米载体药物递送系统(NDDS)在脑药物递送方面受到越来越多的关注,因为它有助于药物通过血脑屏障并提高生物利用度。这可能对治疗抑郁症有益。由于纳米载体的粒径和物理化学性质,它有望改善抗抑郁药的稳定性和溶解度,从而提高药物浓度。此外,配体修饰的纳米载体可作为靶向药物直接释放系统,减少药物副作用。本综述的目的是提供对纳米载体药物递送系统和不同摄入途径中相关抗抑郁药的最新了解,为抑郁症患者的治疗奠定基础。
    Depression is a chronic mental disorder characterized by persistent low mood and loss of interest. Treatments for depression are varied but may not be sufficient cure. Drug-based treatment regimens have drawbacks such as slow onset of action, low bioavailability, and drug side effects. Nanocarrier Drug Delivery Systems (NDDS) has received increasing attention for brain drug delivery since it assists the drug through the blood-brain barrier and improves bioavailability, which may be beneficial for treating depression. Due to the particle size and physicochemical properties of nanocarriers, it presents a promise to improve the stability and solubility of antidepressants, thereby enhancing the drug concentration. Moreover, ligand-modified nanocarriers can be taken as a target direct medicines release system and reduce drug side effects. The purpose of the present review is to provide an up-to-date understanding of the Nanocarrier drug delivery system and relevant antidepressants in different routes of ingestion, to lay a foundation for the treatment of patients with depression.
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  • 文章类型: Journal Article
    甲基强的松龙(MP)的强抗炎作用是包括急性脊髓损伤(SCI)在内的各种严重病例的必要治疗方法。然而,人们对国会议员的不利影响表示担忧,这也严重限制了其临床应用。天然多酚,由于其丰富的酚羟基化学性质,可以形成动态结构,而无需额外的修改,在病变部位实现靶向富集和药物释放,使他们成为一个非常有前途的载体。考虑到MP的临床应用挑战,天然多酚平台用于MP的靶向和有效递送,减少其全身副作用。体外和SCI模型均证明多酚作为递送MP的载体具有多种优势:(1)在给药后2小时内在受伤部位实现了最大富集,满足了疾病早期治疗的愿望;(2)MP的无痕释放;(3)减少其副作用;(4)赋予治疗系统新的抗氧化特性,这也是疾病治疗需要解决的一个方面。这项研究强调了基于天然多酚的强大传递系统可以成功克服MP治疗障碍的前景,为其广泛的临床应用提供了可能。
    The strong anti-inflammatory effect of methylprednisolone (MP) is a necessary treatment for various severe cases including acute spinal cord injury (SCI). However, concerns have been raised regarding adverse effects from MP, which also severely limits its clinical application. Natural polyphenols, due to their rich phenolic hydroxyl chemical properties, can form dynamic structures without additional modification, achieving targeted enrichment and drug release at the disease lesion, making them a highly promising carrier. Considering the clinical application challenges of MP, a natural polyphenolic platform is employed for targeted and efficient delivery of MP, reducing its systemic side effects. Both in vitro and SCI models demonstrated polyphenols have multiple advantages as carriers for delivering MP: (1) Achieved maximum enrichment at the injured site in 2 h post-administration, which met the desires of early treatment for diseases; (2) Traceless release of MP; (3) Reducing its side effects; (4) Endowed treatment system with new antioxidative properties, which is also an aspect that needs to be addressed for diseases treatment. This study highlighted a promising prospect of the robust delivery system based on natural polyphenols can successfully overcome the barrier of MP treatment, providing the possibility for its widespread clinical application.
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  • 文章类型: Journal Article
    与传统癌症治疗方式相关的局限性,特别是对于乳腺癌,强调必须开发更安全、更高效的药物输送系统。出现的有希望的策略是化学疗法与气体疗法的结合。在本研究中,我们通过气体扩散反应合成了负载姜黄素的无定形碳酸钙纳米颗粒(Cur-CaCO3)。随后,采用“一步”乙醇注射法制备负载L-精氨酸的脂质涂层碳酸钙纳米颗粒(Cur-CaCO3@LA-Lip),旨在利用化疗和一氧化氮的协同作用来增强抗肿瘤疗效。透射电子显微镜分析显示Cur-CaCO3@LA-Lip纳米颗粒是亚球形的,具有包封外周的独特脂质层。傅里叶变换红外光谱,X射线粉末衍射,和差示扫描量热法结果证实了Cur-CaCO3@LA-Lip的成功合成。纳米颗粒表现出姜黄素8.89%和L-精氨酸3.1%的显著载药量。体外和体内评估表明,Cur-CaCO3@LA-Lip纳米颗粒促进姜黄素的持续释放,并表现出高细胞摄取,大量的肿瘤积累,和优良的生物相容性。此外,纳米粒子显示出强大的细胞毒性和强大的抗肿瘤功效,表明它们作为乳腺癌治疗的强大候选者的潜力。
    The limitations associated with conventional cancer treatment modalities, particularly for breast cancer, underscore the imperative for developing safer and more productive drug delivery systems. A promising strategy that has emerged is the combination of chemotherapy with gas therapy. We synthesized curcumin-loaded amorphous calcium carbonate nanoparticles (Cur-CaCO3) via a gas diffusion reaction in the present study. Subsequently, a \"one-step\" ethanol injection method was employed to fabricate lipid-coated calcium carbonate nanoparticles (Cur-CaCO3@LA-Lip) loaded with L-arginine, aimed at harnessing the synergistic effects of chemotherapy and nitric oxide to enhance antitumor efficacy. Transmission electron microscopy analysis revealed that Cur-CaCO3@LA-Lip nanoparticles were subspherical with a distinct lipid layer encapsulating the periphery. Fourier transform infrared spectroscopy, X-ray powder diffraction, and differential scanning calorimetry results confirmed the successful synthesis of Cur-CaCO3@LA-Lip. The nanoparticles exhibited significant drug loading capacities of 8.89% for curcumin and 3.1% for L-arginine. In vitro and in vivo assessments demonstrated that Cur-CaCO3@LA-Lip nanoparticles facilitated sustained release of curcumin and exhibited high cellular uptake, substantial tumor accumulation, and excellent biocompatibility. Additionally, the nanoparticles showed robust cytotoxicity and potent antitumor efficacy, suggesting their potential as a formidable candidate for breast cancer therapy.
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  • 文章类型: Journal Article
    在这项研究中,制备水包油纳米乳液,各向同性的油混合物,表面活性剂,和助表面活性剂。纳米乳剂表现出稳定的结构并且能够有效地包封疏水性药物如多柔比星(Dox)。与聚合物胶束相比,纳米乳液对Dox表现出增强的稳定性和负载能力。此外,纳米乳液在14天内稳定释放Dox,在最初的24小时内释放了51.6%,在随后的时期释放了高达80%。这些特性表明,纳米乳液可以减轻与Dox爆发释放相关的副作用,从而提高治疗效果和安全性。此外,与用游离Dox处理的心肌细胞相比,纳米乳液处理的心肌细胞显示出增加的活力,表明纳米乳剂减轻Dox诱导的心脏毒性的潜力。总的来说,纳米乳剂有望成为改善癌症治疗结果的多功能和有效的药物载体。
    In this study, oil-in-water nanoemulsions are prepared, an isotropic mixture of oil, surfactant, and cosurfactants. The nanoemulsions exhibit stable structures and are capable of efficiently encapsulating hydrophobic drugs such as doxorubicin (Dox). Compared to polymeric micelles, nanoemulsions demonstrate enhanced stability and loading capacity for Dox. Furthermore, nanoemulsions release Dox steadily over 14 days, with 51.6% released within the initial 24 h and up to 80% over the subsequent period. These properties suggest that nanoemulsions can mitigate the side effects related to the burst release of Dox, thereby improving therapeutic efficacy and safety. Additionally, nanoemulsion-treated cardiomyocytes show increased viability compared to those treated with free Dox, indicating the potential of nanoemulsions to alleviate Dox-induced cardiotoxicity. Overall, nanoemulsions hold promise as versatile and efficient drug carriers for improving cancer treatment outcomes.
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  • 文章类型: Journal Article
    目前,多发性骨髓瘤(MM)是一种常见的造血系统恶性肿瘤,以其隐匿的起病和不利的预后而闻名。最近开发的用于MM的化疗药物已显示出有希望的治疗结果。然而,克服传统临床药物治疗的缺点,比如脱靶效应,多重耐药性,和全身毒性,靶向药物递送系统正在优化常规药物,以可控的速率精确递送到指定地点,争取最大的疗效和安全性,为MM治疗提供了一种有希望的方法。这篇综述将深入研究抗体-药物缀合物的优异性能,肽-药物缀合物,适体-药物缀合物,和纳米载体药物递送系统在MM的临床前研究或临床试验中,并监测其治疗过程中的不良反应。
    Currently, multiple myeloma (MM) is a prevalent hematopoietic system malignancy, known for its insidious onset and unfavorable prognosis. Recently developed chemotherapy drugs for MM have exhibited promising therapeutic outcomes. Nevertheless, to overcome the shortcomings of traditional clinical drug treatment, such as off-target effects, multiple drug resistance, and systemic toxicity, targeted drug delivery systems are optimizing the conventional pharmaceuticals for precise delivery to designated sites at controlled rates, striving for maximal efficacy and safety, presenting a promising approach for MM treatment. This review will delve into the outstanding performance of antibody-drug conjugates, peptide-drug conjugates, aptamer-drug conjugates, and nanocarrier drug delivery systems in preclinical studies or clinical trials for MM and monitor their adverse reactions during treatment.
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  • 文章类型: Journal Article
    免疫疗法因其副作用小,一直是研究的热点,持久功效,和广泛的抗肿瘤谱。最近,基于NK细胞的免疫治疗因其独特的肿瘤识别和根除免疫学特性以及移植物抗宿主病和细胞因子风暴的低风险而受到广泛关注。在药物输送系统(DDS)的配合下,NK细胞通过在载药DDS施用后调节其表面上的激活和抑制信号的平衡来激活杀肿瘤活性。此外,NK细胞或NK衍生的外泌体也可以用作药物载体进行不同的修饰以促进NK活化并发挥抗肿瘤作用。在这次审查中,我们首先介绍了NK细胞的来源和分类,并描述了其表面常见的激活和抑制受体。然后,我们总结了通过各种DDS激活体内NK细胞的策略。最后,并对NK细胞在肿瘤免疫治疗中的应用前景进行了展望。
    Immunotherapy has been a research hotspot due to its low side effects, long-lasting efficacy, and wide anti-tumor spectrum. Recently, NK cell-based immunotherapy has gained broad attention for its unique immunological character of tumor identification and eradication and low risk of graft-versus-host disease and cytokine storm. With the cooperation of a drug delivery system (DDS), NK cells activate tumoricidal activity by adjusting the balance of the activating and inhibitory signals on their surface after drug-loaded DDS administration. Moreover, NK cells or NK-derived exosomes can also be applied as drug carriers for distinct modification to promote NK activation and exert anti-tumor effects. In this review, we first introduce the source and classification of NK cells and describe the common activating and inhibitory receptors on their surface. Then, we summarize the strategies for activating NK cells in vivo through various DDSs. Finally, the application prospects of NK cells in tumor immunotherapy are also discussed.
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  • 文章类型: Journal Article
    胶质瘤是颅内最常见的原发性肿瘤,它是由大脑和脊髓中神经胶质细胞的恶性转化形成的。它具有发病率高的特点,复发率高,死亡率高,治愈率低。神经胶质瘤的治疗包括手术切除,化疗和放疗。由于脑组织生物屏障的阻塞,很难达到预期的治疗效果。为了解决大脑天然屏障的局限性,提高治疗效果,研究人员已经有效地将脑靶向药物递送系统(DDS)应用于神经胶质瘤治疗.聚酰胺胺(PAMAM)树枝状聚合物,作为支化大分子结构,代表神经胶质瘤治疗研究的有希望的候选人。本文就基于PAMAM的DDS在脑胶质瘤治疗中的应用作一综述,突出它们的物理化学特征,结构特性以及毒性和安全概况的概述。
    Glioma is the most common primary intracranial tumor, which is formed by the malignant transformation of glial cells in the brain and spinal cord. It has the characteristics of high incidence, high recurrence rate, high mortality and low cure rate. The treatments for glioma include surgical removal, chemotherapy and radiotherapy. Due to the obstruction of the biological barrier of brain tissue, it is difficult to achieve the desired therapeutic effects. To address the limitations imposed by the brain\'s natural barriers and enhance the treatment efficacy, researchers have effectively used brain-targeted drug delivery systems (DDSs) in glioma therapy. Polyamidoamine (PAMAM) dendrimers, as branched macromolecular architectures, represent promising candidates for studies in glioma therapy. This review focuses on PAMAM-based DDSs in the treatment of glioma, highlighting their physicochemical characteristics, structural properties as well as an overview of the toxicity and safety profiles.
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  • 文章类型: Journal Article
    炎症性肠病(IBD)是一种慢性,以肠粘膜反复发炎为特征的非特异性炎症。然而,现有的IBD治疗无效且具有严重的副作用。IBD的病因是多因素的,包括免疫,遗传,环境,饮食,和微生物因素。随着纳米技术的发展,基于特定靶向方法开发的纳米颗粒(NP)显示出巨大的潜力。纳米颗粒被定义为尺寸在1和100nm之间的颗粒。根据它们的尺寸和表面功能,NP表现出不同的性质。多种纳米颗粒类型已被用作治疗炎症性肠病(IBD)的药物载体。在实验模型中观察到令人鼓舞的结果。它们增加了药物的生物利用度,并实现了靶向药物递送,促进局部治疗,从而提高疗效。然而,从纳米医学到临床应用的转化仍然存在许多挑战,包括增强的配方和制备技术,增强药物安全性,等等。在未来,科学家和临床医生有必要合作研究疾病机制,开发新的药物输送策略,筛选新的纳米药物。然而,从纳米医学到临床应用的转化仍然存在许多挑战,包括增强的配方和制备技术,增强药物安全性,等等。在未来,科学家和临床医生有必要合作研究疾病机制,开发新的药物输送策略,筛选新的纳米药物。
    Inflammatory bowel disease (IBD) is a chronic, non-specific inflammatory condition characterized by recurring inflammation of the intestinal mucosa. However, the existing IBD treatments are ineffective and have serious side effects. The etiology of IBD is multifactorial and encompasses immune, genetic, environmental, dietary, and microbial factors. The nanoparticles (NPs) developed based on specific targeting methodologies exhibit great potential as nanotechnology advances. Nanoparticles are defined as particles between 1 and 100 nm in size. Depending on their size and surface functionality, NPs exhibit different properties. A variety of nanoparticle types have been employed as drug carriers for the treatment of inflammatory bowel disease (IBD), with encouraging outcomes observed in experimental models. They increase the bioavailability of drugs and enable targeted drug delivery, promoting localized treatment and thus enhancing efficacy. Nevertheless, numerous challenges persist in the translation from nanomedicine to clinical application, including enhanced formulations and preparation techniques, enhanced drug safety profiles, and so forth. In the future, it will be necessary for scientists and clinicians to collaborate in order to study disease mechanisms, develop new drug delivery strategies, and screen new nanomedicines. Nevertheless, numerous challenges persist in the translation from nanomedicine to clinical application, including enhanced formulations and preparation techniques, enhanced drug safety profiles, and so forth. In the future, it will be necessary for scientists and clinicians to collaborate in order to study disease mechanisms, develop new drug delivery strategies, and screen new nanomedicines.
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  • 文章类型: Journal Article
    靶向干扰素基因刺激因子(STING)途径是克服具有STK11突变的非小细胞肺癌对免疫检查点抑制剂的主要抗性的有希望的策略。我们先前发现二甲双胍增强STING途径,从而促进免疫反应。然而,其在肿瘤中的低浓度限制了其临床应用。这里,我们构建了高介孔Mn基纳米载体负载二甲双胍纳米颗粒(Mn-MSN@Met-MNPs),该纳米载体可主动靶向肿瘤并对释放更高浓度的Mn2+离子和二甲双胍作出反应.NP显著增强了T细胞以杀死具有STK11突变体的肺癌细胞。机制显示增强的STING通路激活促进STING,TBKI,和IRF3磷酸化通过Mn2+离子和二甲双胍从NP释放,从而促进I型干扰素的产生。在体内,NP与PD-1抑制剂组合有效降低肿瘤生长。总的来说,我们开发了一种Mn-MSN@Met-M纳米激活剂,用于增强潜在癌症免疫治疗的免疫激活.
    Targeting the stimulator of interferon genes (STING) pathway is a promising strategy to overcome primary resistance to immune checkpoint inhibitors in non-small cell lung cancer with the STK11 mutation. We previously found metformin enhances the STING pathway and thus promotes immune response. However, its low concentration in tumors limits its clinical use. Here, we constructed high-mesoporous Mn-based nanocarrier loading metformin nanoparticles (Mn-MSN@Met-M NPs) that actively target tumors and respond to release higher concentration of Mn2+ ions and metformin. The NPs significantly enhanced the T cells to kill lung cancer cells with the STK11 mutant. The mechanism shows that enhanced STING pathway activation promotes STING, TBKI, and IRF3 phosphorylation through Mn2+ ions and metformin release from NPs, thus boosting type I interferon production. In vivo, NPs in combination with a PD-1 inhibitor effectively decreased tumor growth. Collectively, we developed a Mn-MSN@Met-M nanoactivator to intensify immune activation for potential cancer immunotherapy.
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