纳米技术在给药系统中的应用

K. Sonamuthu
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Liposomes and polymer micelles were first prepared in 1960’s, and nanoparticles and dendrimers in 1970’s. Colloidal gold particles in nanometer sizes were first prepared by Michael Faraday more than 150 years ago, but were never referred to or associated with nanoparticles or nanotechnology until recently. About three decades ago, colloidal gold particles were conjugated with antibody for target specific staining, known as immunogold staining. Such an application may be considered as a precursor of recent explosive applications of gold particles in nanotechnology. The importance of nanotechnology in drug delivery is in the concept and ability to manipulate molecules and supramolecular structures for producing devices with programmed functions. Conventional liposomes, polymeric micelles, and nanoparticles are now called “nanovehicles,”. Those conventional drug delivery systems would have evolved to the present state regardless of the current nanotechnology revolution. Cancer is one of the most challenging diseases today, and brain cancer is one of the most difficult malignancies to detect and treat mainly because of the difficulty in getting imaging and therapeutic agents across the blood-brain barrier and into the brain. Many investigators have found that nanoparticles hold promise for ferrying such agents into the brain . Apolipoprotein E was suggested to mediate drug transport across the blood-brain barrier . Loperamide, which does not cross the blood-brain barrier but exerts antinociceptive effects after direct injection into the brain, was loaded into human serum albumin nanoparticles and linked to apolipoprotein E. Robust angiogenesis underlies aggressive growth of tumors. Therefore, one of the mechanisms to inhibit angiogenesis is to starve tumor cells. Angiogenesis is regulated through a complex set of mediators and recent evidence shows that integrin αvβ3 and vascular endothelial growth factors (VEGFs) play important regulator roles. The cell adhesion molecules are glycoproteins found on the cell surface that act as receptors for cell-to-cell and cell-to-extracellular matrix adhesion . Recent advancements of the understanding of the cell adhesion molecules has impacted the design and development of drugs (i.e. peptide, proteins) for the potential treatment of cancer, heart and autoimmune diseases. These molecules have important roles in diseases such as cancer, thrombosis and autoimmune diseases such as type-1 diabetes. There also is an exciting possibility to overcome problems of drug resistance in target cells and to facilitating movement of drugs across barriers such as those in the brain. The challenge, however, remains the precise characterization of molecular targets and to ensure that these molecules are expressed only in the targeted organs to prevent effects on healthy tissues. Secondly, it is important to understand the fate of the drugs once delivered to the nucleus and other sensitive cells organelles. 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引用次数: 0

摘要

每隔一段时间,就会出现一个代表新兴科学趋势的新名词。生物技术、基因工程、组织工程、基因治疗、组合化学、高通量筛选和干细胞是过去术语的一些例子。近年来,纳米技术已经成为一个流行的术语,代表了当前科学技术的主要成果。纳米技术仍然不是一项成熟的技术,因此,更合适的说法是纳米科学,通常指的是100纳米或更小尺度的研究。纳米技术的独特之处在于它不仅代表了一个特定的领域,而且代表了从基础材料科学到个人护理应用的广泛学科。纳米技术的一个重要领域是“纳米医学”,它指的是在分子尺度上进行高度特异性的医疗干预,用于诊断、预防和治疗疾病。纳米颗粒有各种形状和大小,它们成为新型药物输送系统中非常重要的元素,称为纳米医学。这些纳米颗粒被开发成适当的尺寸,并被用于靶向体内的目标部位。纳米粒子的发展给给药系统领域带来了革命性的变化。在给药方面,纳米技术才刚刚开始产生影响。然而,目前许多“纳米”药物传递系统都是传统药物传递系统的残余,它们恰好在纳米范围内,如脂质体、聚合物胶束、纳米颗粒、树状大分子和纳米晶体。脂质体和聚合物胶束最早在20世纪60年代制备,纳米颗粒和树状大分子最早在70年代制备。150多年前,迈克尔·法拉第(Michael Faraday)首次制备了纳米尺寸的胶体金颗粒,但直到最近才与纳米粒子或纳米技术联系起来。大约三十年前,胶体金颗粒与抗体结合用于靶特异性染色,称为免疫金染色。这种应用可能被认为是最近金颗粒在纳米技术中的爆炸性应用的先驱。纳米技术在药物传递中的重要性在于其概念和能力,即操纵分子和超分子结构以生产具有编程功能的设备。传统的脂质体、聚合胶束和纳米颗粒现在被称为“纳米载体”。无论当前的纳米技术革命如何,这些传统的药物输送系统都会发展到现在的状态。癌症是当今最具挑战性的疾病之一,脑癌是最难检测和治疗的恶性肿瘤之一,主要是因为很难让成像和治疗药物穿过血脑屏障进入大脑。许多研究人员发现,纳米颗粒有望将这些药物运送到大脑中。载脂蛋白E被认为介导了药物在血脑屏障中的转运。洛哌丁胺不能穿过血脑屏障,但在直接注射到大脑后会产生抗伤害感受作用,它被装载到人血清白蛋白纳米颗粒中,并与载脂蛋白e相关联。因此,抑制血管生成的机制之一是饿死肿瘤细胞。血管生成是通过一系列复杂的介质调节的,最近的证据表明整合素αvβ3和血管内皮生长因子(vegf)在调节血管生成中起着重要的作用。细胞粘附分子是在细胞表面发现的糖蛋白,作为细胞间和细胞外基质粘附的受体。最近对细胞粘附分子的理解取得了进展,影响了用于治疗癌症、心脏病和自身免疫性疾病的药物(即肽、蛋白质)的设计和开发。这些分子在癌症、血栓形成和自身免疫性疾病(如1型糖尿病)等疾病中发挥着重要作用。还有一种令人兴奋的可能性,可以克服靶细胞的耐药性问题,并促进药物跨越障碍(如大脑中的障碍)的运动。然而,挑战仍然是分子靶点的精确表征,并确保这些分子仅在目标器官中表达,以防止对健康组织的影响。其次,了解药物递送到细胞核和其他敏感细胞器后的命运是很重要的。此外,由于纳米系统提高了药物传递的效率,剂量可能需要重新校准。尽管如此,未来仍然是令人兴奋和广阔的。关键词:纳米技术,纳米药物,纳米粒子,脂质体,聚合物胶束,纳米粒子,树状大分子,纳米晶体。 脂质体和聚合物胶束,DOI: 10.7176/APTA/80-02出版日期:2019年10月31日
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Applications of Nanotechnology in Drug Delivery Systems
Every so often, a new term comes along that represents an emerging scientific trend. Biotechnology, genetic engineering, tissue engineering, gene therapy, combinatorial chemistry, high throughput screening, and stem cells are some examples of past terms. Recently, nanotechnology has become a popular term representing the main efforts of the current science and technology. Nanotechnology, which is still not a mature technology and thus, more appropriately called nanoscience, usually refers to research at the scale of 100 nm or less. Nanotechnology is unique in that it represents not just one specific area, but a vast variety of disciplines ranging from basic material science to personal care applications. Thus this technology is very advanced and various researches are a heading in this field very quickly One of the important areas of nanotechnology is “nanomedicine,” which, refers to highly specific medical intervention at the molecular scale for diagnosis, prevention and treatment of diseases The nanoparticles are available in various shapes and sizes and these are  become very important elements in novel drug delivery systems called nanomedicine. These nanoparticles are developed in appropriate sizes and used such that they target at the targeted places in the body. This development of nanoparticles had  brought a revolutionary change in the field of  drug delivery systems.. In drug delivery, nanotechnology is just beginning to make an impact. Many of the current “nano” drug delivery systems, however, are remnants of conventional drug delivery systems that happen to be in the nanometer range, such as liposomes, polymeric micelles, nanoparticles, dendrimers, and nanocrystals. Liposomes and polymer micelles were first prepared in 1960’s, and nanoparticles and dendrimers in 1970’s. Colloidal gold particles in nanometer sizes were first prepared by Michael Faraday more than 150 years ago, but were never referred to or associated with nanoparticles or nanotechnology until recently. About three decades ago, colloidal gold particles were conjugated with antibody for target specific staining, known as immunogold staining. Such an application may be considered as a precursor of recent explosive applications of gold particles in nanotechnology. The importance of nanotechnology in drug delivery is in the concept and ability to manipulate molecules and supramolecular structures for producing devices with programmed functions. Conventional liposomes, polymeric micelles, and nanoparticles are now called “nanovehicles,”. Those conventional drug delivery systems would have evolved to the present state regardless of the current nanotechnology revolution. Cancer is one of the most challenging diseases today, and brain cancer is one of the most difficult malignancies to detect and treat mainly because of the difficulty in getting imaging and therapeutic agents across the blood-brain barrier and into the brain. Many investigators have found that nanoparticles hold promise for ferrying such agents into the brain . Apolipoprotein E was suggested to mediate drug transport across the blood-brain barrier . Loperamide, which does not cross the blood-brain barrier but exerts antinociceptive effects after direct injection into the brain, was loaded into human serum albumin nanoparticles and linked to apolipoprotein E. Robust angiogenesis underlies aggressive growth of tumors. Therefore, one of the mechanisms to inhibit angiogenesis is to starve tumor cells. Angiogenesis is regulated through a complex set of mediators and recent evidence shows that integrin αvβ3 and vascular endothelial growth factors (VEGFs) play important regulator roles. The cell adhesion molecules are glycoproteins found on the cell surface that act as receptors for cell-to-cell and cell-to-extracellular matrix adhesion . Recent advancements of the understanding of the cell adhesion molecules has impacted the design and development of drugs (i.e. peptide, proteins) for the potential treatment of cancer, heart and autoimmune diseases. These molecules have important roles in diseases such as cancer, thrombosis and autoimmune diseases such as type-1 diabetes. There also is an exciting possibility to overcome problems of drug resistance in target cells and to facilitating movement of drugs across barriers such as those in the brain. The challenge, however, remains the precise characterization of molecular targets and to ensure that these molecules are expressed only in the targeted organs to prevent effects on healthy tissues. Secondly, it is important to understand the fate of the drugs once delivered to the nucleus and other sensitive cells organelles. Furthermore, because nanosystems increase efficiency of drug delivery, the doses may need recalibration. Nevertheless, the future remains exciting and wide open. Keywords : Nanotechnology, nanomedicine, nanoparticles, liposomes, polymeric micelles, nanoparticles, dendrimers, and nanocrystals. Liposomes and polymer micelles, DOI : 10.7176/APTA/80-02 Publication date :October 31 st 2019
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