Costa Cláudia Pina, Moreira João Nuno, Sousa Lobo José Manuel, Silva Ana Catarina
UCIBIO/REQUIMTE, Medtech, Laboratory of Pharmaceutical Technology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, Porto 4050-313, Portugal.
CNC - Center for Neuroscience and Cell Biology, Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, Faculty of Medicine (Pólo I), Coimbra 3004-504, Portugal.
Acta Pharm Sin B. 2021 Apr;11(4):925-940. doi: 10.1016/j.apsb.2021.02.012. Epub 2021 Mar 13.
The management of the central nervous system (CNS) disorders is challenging, due to the need of drugs to cross the blood‒brain barrier (BBB) and reach the brain. Among the various strategies that have been studied to circumvent this challenge, the use of the intranasal route to transport drugs from the nose directly to the brain has been showing promising results. In addition, the encapsulation of the drugs in lipid-based nanocarriers, such as solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs) or nanoemulsions (NEs), can improve nose-to-brain transport by increasing the bioavailability and site-specific delivery. This review provides the state-of-the-art of studies with lipid-based nanocarriers (SLNs, NLCs and NEs) for nose-to-brain delivery. Based on the literature available from the past two years, we present an insight into the different mechanisms that drugs can follow to reach the brain after intranasal administration. The results of pharmacokinetic and pharmacodynamics studies are reported and a critical analysis of the differences between the anatomy of the nasal cavity of the different animal species used in studies is carried out. Although the exact mechanism of drug transport from the nose to the brain is not fully understood and its effectiveness in humans is unclear, it appears that the intranasal route together with the use of NLCs, SLNs or NEs is advantageous for targeting drugs to the brain. These systems have been shown to be more effective for nose-to-brain delivery than other routes or formulations with non-encapsulated drugs, so they are expected to be approved by regulatory authorities in the coming years.
由于药物需要穿过血脑屏障（BBB）才能到达大脑，中枢神经系统（CNS）疾病的治疗具有挑战性。在为克服这一挑战而研究的各种策略中，使用鼻内途径将药物从鼻子直接输送到大脑已显示出有前景的结果。此外，将药物封装在基于脂质的纳米载体中，如固体脂质纳米粒（SLNs）、纳米结构脂质载体（NLCs）或纳米乳剂（NEs），可以通过提高生物利用度和实现位点特异性递送来改善鼻脑转运。本综述介绍了基于脂质的纳米载体（SLNs、NLCs和NEs）用于鼻脑递送的研究现状。基于过去两年的现有文献，我们深入探讨了药物在鼻内给药后到达大脑的不同机制。报告了药代动力学和药效学研究的结果，并对研究中使用的不同动物物种鼻腔解剖结构之间的差异进行了批判性分析。尽管药物从鼻子到大脑的确切转运机制尚未完全了解，其在人类中的有效性也尚不清楚，但鼻内途径与使用NLCs、SLNs或NEs一起似乎有利于将药物靶向输送到大脑。这些系统已被证明在鼻脑递送方面比其他途径或未封装药物的制剂更有效，因此预计它们将在未来几年获得监管机构的批准。
