Brain Institute-Instituto Israelita de Ensino e Pesquisa Albert Einstein, Morumbi-São Paulo, SP, Brazil.
Neuropeptides. 2011 Oct;45(5):309-16. doi: 10.1016/j.npep.2011.03.001. Epub 2011 Apr 7.
This review shows some classical applications of peptides and suggests there is great promise for the treatment of various central nervous system diseases. Actually, peptides are considered the new generation of biologically active tools because they are key regulators in cellular and intercellular physiological responses, which possess enormous potential for the treatment of various diseases. In spite of their clinical potential, native peptides have seen limited use due to their poor bioavailability and low stability in physiological conditions. Moreover, most peptide or protein pharmaceuticals currently in use are delivered by invasive routes such as via subcutaneous injection. Considerable efforts have been made to design new drugs based on peptides and recent developments in technology and science have provided the means and opportunity to produce a stable as well as controlled-release form of peptide and protein drugs to combat poorly controlled diseases and to increase patients' quality of life. A major challenge in this regard, however, is the delivery of peptides over the blood-brain barrier. This review gives an overview of some strategies used to improve both bioavailability and uptake of peptide drugs for delivery into the brain. Indeed, recent findings suggest that the use of peptides by conjugation to a polymer such as nanoparticles can offer tremendous hope in the treatment of brain disorders. The polymer conjugation improves pharmacokinetics by increasing the molecular mass of proteins and peptides and shielding them from proteolytic enzymes. These new strategies will create new opportunities for the future development of neurotherapeutic drugs. In the present review we have focused our attention on the peptide controlled delivery, summarizing literature reports on the use of peptides and nanotechnology for the treatment and diagnosis of brain disorders.
这篇综述展示了一些经典的肽类应用,并表明它们在治疗各种中枢神经系统疾病方面有很大的应用前景。实际上,肽类被认为是新一代具有生物活性的工具,因为它们是细胞和细胞间生理反应的关键调节剂,在治疗各种疾病方面具有巨大的潜力。尽管它们具有临床应用潜力,但由于其在生理条件下的生物利用度差和稳定性低,天然肽的应用受到限制。此外,大多数目前使用的肽或蛋白质药物都是通过侵入性途径给药,如皮下注射。人们已经做出了相当大的努力来设计基于肽的新药,最近的技术和科学发展为生产稳定的、可控释放形式的肽和蛋白质药物提供了手段和机会,以治疗控制不佳的疾病并提高患者的生活质量。然而,这方面的一个主要挑战是将肽递送到血脑屏障。本文综述了一些旨在提高肽类药物生物利用度和脑内摄取的策略。事实上,最近的研究结果表明,通过将肽与聚合物(如纳米粒子)缀合,可以为治疗脑疾病带来巨大希望。聚合物缀合通过增加蛋白质和肽的分子量并使其免受蛋白酶的作用来改善药代动力学。这些新策略将为神经治疗药物的未来发展创造新的机会。在本综述中,我们关注的是肽的控制释放,总结了关于使用肽和纳米技术治疗和诊断脑疾病的文献报道。