Ong Wei-Yi, Shalini Suku-Maran, Costantino Luca
Department of Anatomy, National University of Singapore, Singapore 117597.
Curr Med Chem. 2014;21(37):4247-56. doi: 10.2174/0929867321666140716103130.
Many potential drugs for the treatment of neurological diseases are unable to reach the brain in sufficient enough concentrations to be therapeutic because of the blood brain barrier. On the other hand, direct delivery of drugs to the brain provides the possibility of a greater therapeutic-toxic ratio than with systemic drug delivery. The use of intranasal delivery of therapeutic agents to the brain provides a means of bypassing the blood brain barrier in a non-invasive manner. In this respect, nanosized drug carriers were shown to enhance the delivery of drugs to CNS compared to equivalent drug solution formulations. Neurological conditions that have been studied in animal models that could benefit from nose-to-brain delivery of nanotherapeutics include pain, epilepsy, neurodegenerative disease and infectious diseases. The delivery of drugs to the brain via the nose-to-brain route holds great promise, on the basis of preclinical research by means of drug delivery systems such as polymeric nanoparticles and clinical data related to intranasal delivery to CNS of large molecular weight biologics administered in solution, but safety issues about toxicity on nasal mucosa, Np transport into the brain, delivery only to specific brain regions and variability in the adsorbed dose still represent research topics that need to be considered, with a view of clinical translation of these delivery systems.
由于血脑屏障的存在，许多用于治疗神经疾病的潜在药物无法以足够的浓度到达大脑从而发挥治疗作用。另一方面，与全身给药相比，直接将药物递送至大脑可提供更高的治疗毒性比。通过鼻腔将治疗剂递送至大脑提供了一种以非侵入性方式绕过血脑屏障的途径。在这方面，与等效的药物溶液制剂相比，纳米级药物载体显示出可增强药物向中枢神经系统的递送。在动物模型中研究过的、可受益于纳米治疗药物经鼻至脑递送的神经疾病包括疼痛、癫痫、神经退行性疾病和传染病。基于聚合物纳米颗粒等药物递送系统的临床前研究以及与溶液中施用的大分子生物制剂经鼻递送至中枢神经系统相关的临床数据，经鼻至脑途径将药物递送至大脑具有很大的前景，但关于鼻黏膜毒性、纳米颗粒进入大脑、仅递送至特定脑区以及吸附剂量的变异性等安全性问题仍是需要考虑的研究课题，以期实现这些递送系统的临床转化。
