Controlled drug delivery

控制药物输送
  • 文章类型: Journal Article
    目前,由于生活质量低,癌症患者的数量一直在增加。出于这个原因,用于治疗癌症的疗法已经得到了专家的很多考虑。许多抗癌药物已被用于治疗癌症患者。然而,立即使用抗癌药物会导致患者不愉快的副作用,并且对应用这些治疗有许多限制。许多聚合物,如纤维素,壳聚糖,聚乙烯醇(PVA),聚丙烯腈(PAN),多肽和聚羟基链烷酸酯具有良好的治疗癌症的性能,但是通过同轴静电纺丝技术生产的基于纳米纤维的靶标和受控药物递送系统具有非凡的性能,例如良好的机械特性,一个很好的释放配置文件,高表面积,和高海绵状和无害的,生物可再生,生物友好,高度可降解,并且可以非常方便地以工业规模生产。因此,通过同轴静电纺丝生产的纳米纤维可以设计为靶向特定的癌细胞或组织。通过改变纳米纤维的组成和性能,研究人员可以控制治疗剂的释放动力学,并增强其在肿瘤部位的积累,同时将全身毒性降至最低。同轴电纺纳米纤维的核-壳结构允许治疗剂随时间的受控和持续释放。这种受控释放曲线可以通过在肿瘤微环境内维持治疗药物浓度延长的时间来提高癌症治疗的功效。
    Currently, the number of patients with cancer is expanding consistently because of a low quality of life. For this reason, the therapies used to treat cancer have received a lot of consideration from specialists. Numerous anticancer medications have been utilized to treat patients with cancer. However, the immediate utilization of anticancer medicines leads to unpleasant side effects for patients and there are many restrictions to applying these treatments. A number of polymers like cellulose, chitosan, Polyvinyl Alcohol (PVA), Polyacrylonitrile (PAN), peptides and Poly (hydroxy alkanoate) have good properties for the treatment of cancer, but the nanofibers-based target and controlled drug delivery system produced by the co-axial electrospinning technique have extraordinary properties like favorable mechanical characteristics, an excellent release profile, a high surface area, and a high sponginess and are harmless, bio-renewable, biofriendly, highly degradable, and can be produced very conveniently on an industrial scale. Thus, nanofibers produced through coaxial electrospinning can be designed to target specific cancer cells or tissues. By modifying the composition and properties of the nanofibers, researchers can control the release kinetics of the therapeutic agent and enhance its accumulation at the tumor site while minimizing systemic toxicity. The core-shell structure of coaxial electrospun nanofibers allows for a controlled and sustained release of therapeutic agents over time. This controlled release profile can improve the efficacy of cancer treatment by maintaining therapeutic drug concentrations within the tumor microenvironment for an extended period.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

  • 文章类型: Journal Article
    仿生凝胶是旨在模拟自然生物系统的特性和功能的合成材料,如组织和细胞环境。本手稿探讨了可注射仿生凝胶在生物医学应用中的进展和未来方向,并强调了水凝胶在伤口愈合中的巨大潜力,组织再生,和受控的药物输送,由于其增强的生物相容性,多功能性,和机械性能。尽管取得了这些进步,挑战,如机械弹性,受控的降解速率,和可扩展的制造仍然存在。本手稿讨论了正在进行的研究,以优化这些属性,开发具有成本效益的生产技术,整合3D生物打印和纳米技术等新兴技术。通过合作努力应对这些挑战对于释放可注射仿生凝胶在组织工程和再生医学中的全部潜力至关重要。
    Biomimetic gels are synthetic materials designed to mimic the properties and functions of natural biological systems, such as tissues and cellular environments. This manuscript explores the advancements and future directions of injectable biomimetic gels in biomedical applications and highlights the significant potential of hydrogels in wound healing, tissue regeneration, and controlled drug delivery due to their enhanced biocompatibility, multifunctionality, and mechanical properties. Despite these advancements, challenges such as mechanical resilience, controlled degradation rates, and scalable manufacturing remain. This manuscript discusses ongoing research to optimize these properties, develop cost-effective production techniques, and integrate emerging technologies like 3D bioprinting and nanotechnology. Addressing these challenges through collaborative efforts is essential for unlocking the full potential of injectable biomimetic gels in tissue engineering and regenerative medicine.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

  • 文章类型: Journal Article
    肿瘤微环境(TMEs)近年来受到越来越多的关注,因为它们在肿瘤发生中发挥着关键作用。programming,转移,以及对传统癌症治疗方式如化疗的抵制。随着纳米技术的快速发展,已经提出了靶向TMEs异常标志的有效抗肿瘤纳米治疗剂。适当的设计和制造赋予纳米药物主动靶向的能力,TME响应能力,和优化肿瘤的理化性质,从而克服运输障碍并显著提高抗肿瘤治疗益处。这篇综述从TMEs的起源和特征开始,讨论了通过关注生化微环境的调节来调节TMEs的最新策略。如肿瘤酸中毒,缺氧,新陈代谢失调.最后,这篇综述总结了用于TME调节的智能抗癌纳米疗法的开发面临的挑战,并探讨了将疗法与传统疗法结合用于进一步临床转化的有希望的策略。
    Tumor microenvironments (TMEs) have received increasing attention in recent years as they play pivotal roles in tumorigenesis, progression, metastases, and resistance to the traditional modalities of cancer therapy like chemotherapy. With the rapid development of nanotechnology, effective antineoplastic nanotherapeutics targeting the aberrant hallmarks of TMEs have been proposed. The appropriate design and fabrication endow nanomedicines with the abilities for active targeting, TMEs-responsiveness, and optimization of physicochemical properties of tumors, thereby overcoming transport barriers and significantly improving antineoplastic therapeutic benefits. This review begins with the origins and characteristics of TMEs and discusses the latest strategies for modulating the TMEs by focusing on the regulation of biochemical microenvironments, such as tumor acidosis, hypoxia, and dysregulated metabolism. Finally, this review summarizes the challenges in the development of smart anti-cancer nanotherapeutics for TME modulation and examines the promising strategies for combination therapies with traditional treatments for further clinical translation.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

  • 文章类型: Journal Article
    细菌感染的伤口愈合受到抗生素耐药性和持续炎症的极大阻碍。开发具有有效抗菌性能并可同时加速伤口愈合过程以克服上述挑战的多功能纳米复合材料至关重要。在这里,我们首次通过在AgNWs上蚀刻ZIF-67,制备了卵黄壳结构的Ag纳米线(NWs)@无定形中空ZIF-67,用于感染的伤口愈合。纳米复合材料中无定形ZIF-67的蚀刻中空结构使其成为装载促进愈合药物的有希望的平台。我们广泛研究了姜黄素(CCM)负载的纳米复合材料(AgNWs@C-HZ67)的抗菌和促进愈合的特性。AgNWs,是具有等离子体激元效应的贵金属材料,可以吸收广泛的自然光并将其转化为热能。这种光热转化进一步改善了暴露于光时抗菌成分和伤口愈合药物的释放。在感染伤口的愈合过程中,与伤口渗出物直接接触并在光照射的影响下,AgNWs@C-HZ67释放出Ag和Co离子。同时,装载的CCM泄漏出来修复感染的伤口。暴露于白光时,AgNWs@C-HZ67组对大肠杆菌和金黄色葡萄球菌的最低抑菌浓度分别降至3和3μgml-1。此外,感染伤口愈合的体内评估表明,结合AgNWs@C-HZ67与光显著加速伤口愈合过程,到第6天达到70%的愈合,到第8天几乎完全愈合。这种先进的纳米复合材料,由具有抗菌和促进生长特性的成分组成,提供了一个保险箱,有效和临床翻译的解决方案,用于加速感染伤口的愈合过程。
    Bacteria-infected wounds healing has been greatly hindered by antibiotic resistance and persistent inflammation. It is crucial to develop multifunctional nanocomposites that possess effective antibacterial properties and can simultaneously accelerate the wound healing process to overcome the above challenges. Herein, we prepared a yolk-shell structured Ag nanowires (NWs)@amorphous hollow ZIF-67 by etching ZIF-67 onto the Ag NWs for infected wound healing for the first time. The etched hollow structure of amorphous ZIF-67 in the nanocomposite makes it a promising platform for loading healing-promoting drugs. We extensively studied the antibacterial and healing-promoting properties of the curcumin (CCM)-loaded nanocomposite (Ag NWs@C-HZ67). Ag NWs, being noble metal materials with plasmonic effects, can absorb a broad range of natural light and convert it to thermal energy. This photothermal conversion further improves the release of antibacterial components and wound healing drugs when exposed to light. During the healing process of an infected wound, Ag and Co ions were released from Ag NWs@C-HZ67 upon direct contact with the wound exudate and under the influence of light irradiation. Simultaneously, the loaded CCM leaked out to repair the infected wound. The minimum inhibitory concentrations of the Ag NWs@C-HZ67 groups against Escherichia coli and Staphylococcus aureus bacteria decreased to 3 and 3 μg ml-1 when exposed to white light. Furthermore, an in vivo assessment of infected wound healing demonstrated that combining Ag NWs@C-HZ67 with light significantly accelerated the wound healing process, achieving 70% healing by the 6th day and almost complete healing by the 8th day. This advanced nanocomposite, consisting of components that possess antibacterial and growth-promoting properties, offers a safe, effective and clinically-translatable solution for accelerating the healing process of infected wounds.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

  • 文章类型: Journal Article
    缺血性中风引起的神经损伤是造成永久性残疾和死亡的主要原因。目前可用的神经保护药物主要由于短的循环半衰期和差的血脑屏障(BBB)渗透性而未能实现期望的治疗功效。为此,开发了一种负载依达拉奉的pH/谷胱甘肽(pH/GSH)双响应聚(氨基酸)纳米凝胶(NG/EDA),以改善EDA的神经保护作用。纳米凝胶是由酸性和EDA诱导的高水平GSH微环境触发的,这使得EDA在缺血性损伤部位的选择性和持续释放成为可能。NG/EDA表现出均匀的亚球形形态,平均流体动力学直径为112.3±8.2nm。NG/EDA在永久性大脑中动脉闭塞(pMCAO)小鼠的脑缺血损伤部位有效积累,显示出有效的BBB穿越特征。值得注意的是,具有50µMEDA的NG/EDA通过抑制铁凋亡而显着增加了氧和葡萄糖剥夺后的神经元存活率(29.3%)。此外,给予NG/EDA7d可将梗死体积显着降低至22.2%±7.2%,并将神经行为评分从9.0±0.6降低至2.0±0.8。这种pH/GSH双响应纳米平台可能为缺血性中风和其他中枢神经系统疾病的神经保护提供独特且有前途的方式。
    Neurological injury caused by ischemic stroke is a major cause of permanent disability and death. The currently available neuroprotective drugs fail to achieve desired therapeutic efficacy mainly due to short circulation half-life and poor blood-brain barrier (BBB) permeability. For that, an edaravone-loaded pH/glutathione (pH/GSH) dual-responsive poly(amino acid) nanogel (NG/EDA) was developed to improve the neuroprotection of EDA. The nanogel was triggered by acidic and EDA-induced high-level GSH microenvironments, which enabled the selective and sustained release of EDA at the site of ischemic injury. NG/EDA exhibited a uniform sub-spherical morphology with a mean hydrodynamic diameter of 112.3 ± 8.2 nm. NG/EDA efficiently accumulated at the cerebral ischemic injury site of permanent middle cerebral artery occlusion (pMCAO) mice, showing an efficient BBB crossing feature. Notably, NG/EDA with 50 µM EDA significantly increased neuron survival (29.3%) following oxygen and glucose deprivation by inhibiting ferroptosis. In addition, administering NG/EDA for 7 d significantly reduced infarct volume to 22.2% ± 7.2% and decreased neurobehavioral scores from 9.0 ± 0.6 to 2.0 ± 0.8. Such a pH/GSH dual-responsive nanoplatform might provide a unique and promising modality for neuroprotection in ischemic stroke and other central nervous system diseases.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

  • 文章类型: Journal Article
    该手稿提出了一种创新的方法,通过利用直链淀粉作为新型药物递送载体来减轻与非甾体类抗炎药(NSAIDs)相关的胃肠道逆境。直链淀粉的内在属性,比如它的结构独特性,生物相容性和生物降解性,以及它与不同药物分子形成包合物的能力,经过精心探索。通过对直链淀粉和溃疡性非甾体抗炎药的全面理化分析,阐明了直链淀粉作为溃疡性NSAIDs对胃肠道区域的保护性载体的可行性。这篇综述进一步讨论了基于直链淀粉的药物递送系统在胃溃疡管理中的潜在治疗优势。通过提供受控的释放动力学和增强的生物利用度,这些系统为开发更有效的溃疡疗法提供了有希望的前景。
    This manuscript proposes an innovative approach to mitigate the gastrointestinal adversities linked with nonsteroidal anti-inflammatory drugs (NSAIDs) by exploiting amylose as a novel drug delivery carrier. The intrinsic attributes of V-amylose, such as its structural uniqueness, biocompatibility and biodegradability, as well as its capacity to form inclusion complexes with diverse drug molecules, are meticulously explored. Through a comprehensive physicochemical analysis of V-amylose and ulcerogenic NSAIDs, the plausibility of amylose as a protective carrier for ulcerogenic NSAIDs to gastrointestinal regions is elucidated. This review further discusses the potential therapeutic advantages of amylose-based drug delivery systems in the management of gastric ulcers. By providing controlled release kinetics and enhanced bioavailability, these systems offer promising prospects for the development of more effective ulcer therapies.
    [Box: see text].
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

  • 文章类型: Journal Article
    壳聚糖,是一种生物相容性和粘膜粘附性的多糖,是用于药物递送的最优选的水凝胶形成材料之一。本研究的目的是获得基于低分子量壳聚糖的喷雾干燥微粒,并研究其作为口服活性药物盐酸苄达明的货物系统的潜在应用。获得三种类型的颗粒:原始壳聚糖颗粒(三种不同浓度),交联与三磷酸钠(NaTPP)颗粒(在三个不同的壳聚糖:NaTPP比例),和涂有甘露醇的颗粒(三种不同的壳聚糖:甘露醇比例),它们的尺寸范围都在1到10µm之间。基于配制的水凝胶颗粒的加载效率和产率,选择每种类型的一个模型用于进一步研究交联剂或赋形剂对凝胶结构性质的影响。通过扫描电子显微镜检查了空的和盐酸苄达明的壳聚糖颗粒的形态,它非常规则和球形。通过傅立叶变换红外光谱法研究了样品中的相互作用和组成。通过差示扫描量热法和X射线粉末衍射测试了药物和含药聚合物基质的热稳定性和相态,揭示药物经历了相变。在模拟唾液缓冲液(pH=6.8)中对所选的基于凝胶的结构进行了药物释放动力学研究,并对该过程进行了数学建模,表明威布尔模型是最合适的模型。
    Chitosan, being a biocompatible and mucoadhesive polysaccharide, is one of the most preferred hydrogel-forming materials for drug delivery. The objectives of the present study are to obtain spray-dried microparticles based on low-molecular-weight chitosan and study their potential application as cargo systems for the orally active drug benzydamine hydrochloride. Three types of particles are obtained: raw chitosan particles (at three different concentrations), cross-linked with sodium tripolyphosphate (NaTPP) particles (at three different chitosan:NaTPP ratios), and particles coated with mannitol (at three different chitosan:mannitol ratios), all of them in the size range between 1 and 10 µm. Based on the loading efficiency and the yields of the formulated hydrogel particles, one model of each type is chosen for further investigation of the effect of the cross-linker or the excipient on the properties of the gel structures. The morphology of both empty and benzydamine hydrochloride-loaded chitosan particles was examined by scanning electron microscopy, and it was quite regular and spherical. Interactions and composition in the samples are investigated by Fourier-transformed infrared spectroscopy. The thermal stability and phase state of the drug and drug-containing polymer matrixes were tested by differential scanning calorimetry and X-ray powdered diffraction, revealing that the drug underwent a phase transition. A drug release kinetics study of the chosen gel-based structures in simulated saliva buffer (pH = 6.8) and mathematical modeling of the process were performed, indicating the Weibull model as the most appropriate one.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

  • 文章类型: Journal Article
    有机磷(OP)毒性与乙酰胆碱酯酶(AChE)活性的抑制有关,在神经传递过程中起着关键作用。在这项工作中,我们报告了不同的锌沸石咪唑酯骨架(ZIFs)作为抗OP中毒的潜在解毒剂的能力。Zn-L配位键(L=嘌呤,苯并咪唑,咪唑,或2-甲基咪唑)对G型神经毒剂模型化合物二异丙基氟磷酸盐(DIFP)和二异丙基氯磷酸盐敏感,导致P-X(X=F或Cl)键分解成无毒的二异丙基磷酸酯。P-X水解伴随着ZIF结构降解(Zn-咪唑酯键水解),伴随的咪唑酯接头和锌离子的释放代表高达95%的ZIF颗粒溶解。所递送的咪唑酯对OP@AChE加合物的亲核攻击引起AChE酶促功能的恢复。P-X键分解,ZIF结构退化,AChE的再活化依赖于咪唑酯接头的亲核性,框架拓扑,和颗粒大小。对于20nm的Zn(2-甲基咪唑)2(sodZIF-8)纳米颗粒(NPs),DIFP降解半衰期为2.6分钟,AChE活性在1小时内完全恢复,可获得最佳性能。20nmsodZIF-8NPs无神经毒性,如体外神经母细胞瘤细胞培养物活力测试所证明的。
    Organophosphate (OP) toxicity is related to inhibition of acetylcholinesterase (AChE) activity, which plays a key role in the neurotransmission process. In this work, we report the ability of different zinc zeolitic imidazolate frameworks (ZIFs) to behave as potential antidotes against OP poisoning. The Zn-L coordination bond (L = purine, benzimidazole, imidazole, or 2-methylimidazole) is sensitive to the G-type nerve agent model compounds diisopropylfluorophosphate (DIFP) and diisopropylchlorophosphate, leading to P-X (X = F or Cl) bond breakdown into nontoxic diisopropylphosphate. P-X hydrolysis is accompanied by ZIF structural degradation (Zn-imidazolate bond hydrolysis), with the concomitant release of the imidazolate linkers and zinc ions representing up to 95% of ZIF particle dissolution. The delivered imidazolate nucleophilic attack on the OP@AChE adduct gives rise to the recovery of AChE enzymatic function. P-X bond breakdown, ZIF structural degradation, and AChE reactivation are dependent on imidazolate linker nucleophilicity, framework topology, and particle size. The best performance is obtained for 20 nm nanoparticles (NPs) of Zn(2-methylimidazolate)2 (sod ZIF-8) exhibiting a DIFP degradation half-life of 2.6 min and full recovery of AChE activity within 1 h. 20 nm sod ZIF-8 NPs are not neurotoxic, as proven by in vitro neuroblastoma cell culture viability tests.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

  • 文章类型: Editorial
    暂无摘要。
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

  • 文章类型: Journal Article
    小儿声门下狭窄(SGS)是由长时间插管引起的,其中疤痕组织导致气道狭窄,需要进行侵入性手术。我们最近发现,调节喉气管微生物组可以预防SGS。在这里,我们展示了我们正在申请专利的抗菌肽洗脱气管导管(AMP-ET)如何有效调节局部气道微生物群,从而降低炎症和狭窄消退.
    我们制造了涂有聚合物AMP洗脱层的鼠标大小的ET,定量AMP释放超过10天,并验证了浮游和生物膜驻留细菌对金黄色葡萄球菌和铜绿假单胞菌的杀菌活性。离体测试:我们将AMP-ET和ET对照插入C57BL/6小鼠切除的喉气管复合物(LTCs)中,并在24小时后评估生物膜的形成。体内测试:将AMP-ET和ET对照插入假手术或SGS诱导的LTC中,然后将其皮下植入受体小鼠体内,7天后评估免疫反应和SGS严重程度。
    我们实现了可重复的,以1.16µg/天的线性AMP释放,导致体外和离体强烈的细菌抑制作用。在体内,SGS诱导的LTC表现出典型的狭窄性瘢痕组织增厚,而AMP-ET的使用消除了狭窄。值得注意的是,SGS气道表现出T细胞和巨噬细胞的高浸润,用AMP-ET治疗逆转。这表明通过调节微生物组,AMP-ET减少巨噬细胞活化和抗原特异性T细胞应答解决狭窄进展。
    我们开发了一种AMP-ET平台,该平台通过气道微生物组调节在体内减少T细胞和巨噬细胞反应并减少SGS。
    在线版本包含补充材料,可在10.1007/s12195-023-00769-9获得。
    UNASSIGNED: Pediatric subglottic stenosis (SGS) results from prolonged intubation where scar tissue leads to airway narrowing that requires invasive surgery. We have recently discovered that modulating the laryngotracheal microbiome can prevent SGS. Herein, we show how our patent-pending antimicrobial peptide-eluting endotracheal tube (AMP-ET) effectively modulates the local airway microbiota resulting in reduced inflammation and stenosis resolution.
    UNASSIGNED: We fabricated mouse-sized ETs coated with a polymeric AMP-eluting layer, quantified AMP release over 10 days, and validated bactericidal activity for both planktonic and biofilm-resident bacteria against Staphylococcus aureus and Pseudomonas aeruginosa. Ex vivo testing: we inserted AMP-ETs and ET controls into excised laryngotracheal complexes (LTCs) of C57BL/6 mice and assessed biofilm formation after 24 h. In vivo testing: AMP-ETs and ET controls were inserted in sham or SGS-induced LTCs, which were then implanted subcutaneously in receptor mice, and assessed for immune response and SGS severity after 7 days.
    UNASSIGNED: We achieved reproducible, linear AMP release at 1.16 µg/day resulting in strong bacterial inhibition in vitro and ex vivo. In vivo, SGS-induced LTCs exhibited a thickened scar tissue typical of stenosis, while the use of AMP-ETs abrogated stenosis. Notably, SGS airways exhibited high infiltration of T cells and macrophages, which was reversed with AMP-ET treatment. This suggests that by modulating the microbiome, AMP-ETs reduce macrophage activation and antigen specific T cell responses resolving stenosis progression.
    UNASSIGNED: We developed an AMP-ET platform that reduces T cell and macrophage responses and reduces SGS in vivo via airway microbiome modulation.
    UNASSIGNED: The online version contains supplementary material available at 10.1007/s12195-023-00769-9.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

公众号