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首页> 外文期刊>The Internet Journal of Pharmacology >Brain Targeting Of Nerve Growth Factor Using Poly(Butylcyanoacrylate) Nanoparticles
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Brain Targeting Of Nerve Growth Factor Using Poly(Butylcyanoacrylate) Nanoparticles

机译：使用聚（氰基丙烯酸丙烯酸丁酯）纳米粒子对神经生长因子的脑靶向

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Nerve growth factor (NGF) is essential for the survival of both peripheral ganglion cells and central cholinergic neurons of the basal forebrain. The accelerated loss of central cholinergic neurons during Alzheimer's disease may be a determinant of dementia and this may suggest a possible therapeutic benefit for NGF. However, NGF as all other neurotrophic factors does not significantly penetrate the blood brain barrier, the fact that makes its clinical usefulness depends on the use of suitable carrier system enhances its transport through BBB. The present investigation examines brain delivery of nerve growth factor adsorbed on poly(butylcyanoacryate) nanoparticles coated with polysorbate-80 and testing its effectiveness in reversing of scopolamine-induced amnesia in model of acute amnesia in rats using the passive avoidance reflex (PAR) test. Systemic administration of NGF adsorbed on PBCA-nanoparticles coated with polysorbate-80 successfully reversed scopolamine-induced amnesia and improved recognition and memory in acute amnesia rat model. This appeared in form of significant increase in the mean latent period of (PAR) test in the group of animals treated with NGF adsorbed on PBCA-nanoparticles coated with polysorbate-80 compared with the group treated with free NGF. In summary, these results demonstrate that, using poly(butylcyanoacrylate) nanoparticles coated with polysorbate-80 as a carrier system is effective in targeting NGF to the central nervous system and may optimize the therapy of age-related neurodegenerative diseases. Introduction Nerve growth factor (NGF) which was discovered in the early 1950s, when it was found that; mouse sarcoma tissue transplants in chicken embryos caused an increase in the size of spinal ganglia, was the prototypical neurotrophic factor for many decades (1). It represents the most known and studied trophic factor, which acts on sensory and sympathetic neurons of the peripheral nervous system, and on basal forebrain and striatal cholinergic neurons of the central nervous system (2). The specificity and trophic actions of NGF on these neuronal populations and its efficacy in preventing neurodegeneration have led to its proposal for evaluation in the treatment of neurological diseases such as Alzheimer’s disease, diabetic neuropathies and Huntinton’s disease. Preclinical and clinical studies carried out on animal models and patients with diagnosis of these diseases have revealed satisfactory results (3). The cloning studies demonstrated that; NGF is a member of a gene family dubbed neurotrophins, comprising in mammals also NT-3 and NT-4/5. Currently, six neurotrophins have been isolated: NGF, BDNF, NT-3, NT-4 (also known as NT-5), NT-6, and NT-7. There is substantial evidence that they all arose through successive duplications of the genome of an ancestral chordate (4). The chemical structure of NGF was well studied. It consists of 3 types of subunits, alpha, beta and gamma, which specifically interact to form a 7S, 130,000-molecular weight complex. This complex contains 2 identical 118-amino acid beta-chains, which are solely responsible for nerve growth stimulating activity of NGF (5,6). NGF is synthesized from a precursor peptide “proneutrophin” which has low biological activity compared with the parent members of neurotropins, and is activated by peptide cleavage via enzymatic processes occur at the site of its synthesis (7). After release in target areas of NGF-responsive neurons, nerve growth factor binds to specific cell-surface receptors on the nerve terminals and is retrogradely transported to the cell bodies (8). NGF mediates its cellular responses through binding to two distinct types of cell surface receptors: the high affinity (Trk NTR), family of receptor tyrosine kinases, which exhibit high selectivity for neurotrophin binding, and the low-affinity (p75 NTR) neurotrophin receptor, a member of the tumor necrosis factor receptor family that binds all neurotrophins with similar af
机译：神经生长因子（NGF）对于基底前脑的外周神经节细胞和中枢胆碱能神经元的存活至关重要。阿尔茨海默氏病期间中枢胆碱能神经元的加速丧失可能是痴呆的决定因素，这可能表明对NGF可能具有治疗作用。但是，NGF和所有其他神经营养因子一样，不会显着穿透血脑屏障，其临床实用性取决于使用合适的载体系统，这一事实增强了其通过BBB的转运。本研究通过被动回避反射（PAR）试验检查了大脑吸收被聚山梨酯80涂层的聚（丁基氰基丙烯酸酯）纳米粒子吸附的神经生长因子的能力，并测试了其在逆转东pol碱引起的失忆症中的有效性。全身施用吸附在聚山梨酯80涂层的PBCA纳米颗粒上的NGF可成功逆转东pol碱诱导的健忘症，并改善急性健忘症大鼠模型的识别和记忆力。与用游离NGF处理的组相比，在用NGF处理的动物中，其吸附在涂有聚山梨酯-80的PBCA-纳米颗粒上的NGF组中，其平均潜伏期显着增加。总之，这些结果表明，使用涂有聚山梨酯-80的聚（氰基丙烯酸丁酯）纳米颗粒作为载体系统可有效地将NGF靶向中枢神经系统，并可优化与年龄有关的神经退行性疾病的治疗。简介神经生长因子（NGF）于1950年代初发现，当时被发现。小鼠肉瘤组织移植在鸡胚中引起脊髓神经节大小的增加，是数十年来典型的神经营养因子（1）。它代表了最著名和研究最多的营养因子，它作用于周围神经系统的感觉和交感神经元，以及中枢神经系统的基底前脑和纹状体胆碱能神经元（2）。 NGF对这些神经元群体的特异性和营养作用及其在预防神经退行性变中的功效，导致其提出了对治疗诸如阿尔茨海默氏病，糖尿病性神经病和亨廷顿氏病等神经系统疾病进行评估的提议。对动物模型和诊断出这些疾病的患者进行的临床前和临床研究显示出令人满意的结果（3）。克隆研究表明： NGF是被称为神经营养蛋白的基因家族的成员，在哺乳动物中还包括NT-3和NT-4 / 5。目前，已分离出六个神经营养蛋白：NGF，BDNF，NT-3，NT-4（也称为NT-5），NT-6和NT-7。有大量证据表明，它们都是通过祖先的cho酸盐的基因组的连续复制而产生的（4）。对NGF的化学结构进行了很好的研究。它由3种类型的亚基（α，β和γ）组成，它们特异性地相互作用形成7S，130,000分子量的复合物。该复合物包含2条相同的118个氨基酸的β-链，它们仅负责NGF的神经生长刺激活性（5,6）。 NGF由前体肽“ proneutrophin”合成，与神经营养蛋白的亲本成员相比，该蛋白具有较低的生物学活性，并通过在其合成位点发生的酶促裂解过程被肽裂解激活（7）。在NGF反应性神经元的目标区域释放后，神经生长因子与神经末梢的特定细胞表面受体结合，并逆行转运至细胞体（8）。 NGF通过与两种不同类型的细胞表面受体结合来介导其细胞反应：高亲和力（Trk NTR），受体酪氨酸激酶家族（对神经营养蛋白结合表现出高选择性）和低亲和力（p75 NTR）神经营养蛋白受体，肿瘤坏死因子受体家族的成员，与所有相似的af结合神经营养蛋白

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