Ilić Tanja, Đoković Jelena B, Nikolić Ines, Mitrović Jelena R, Pantelić Ivana, Savić Snežana D, Savić Miroslav M
Department of Pharmaceutical Technology and Cosmetology, University of Belgrade-Faculty of Pharmacy, Vojvode Stepe 450, 11221 Belgrade, Serbia.
Department of Pharmacology, University of Belgrade-Faculty of Pharmacy, Vojvode Stepe 450, 11221 Belgrade, Serbia.
Pharmaceutics. 2023 Jan 29;15(2):443. doi: 10.3390/pharmaceutics15020443.
Contemporary trends in combinatorial chemistry and the design of pharmaceuticals targeting brain disorders have favored the development of drug candidates with increased lipophilicity and poorer water solubility, with the expected improvement in delivery across the blood-brain barrier (BBB). The growing availability of innovative excipients/ligands allowing improved brain targeting and controlled drug release makes the lipid nanocarriers a reasonable choice to overcome the factors impeding drug delivery through the BBB. However, a wide variety of methods, study designs and experimental conditions utilized in the literature hinder their systematic comparison, and thus slows the advances in brain-targeting by lipid-based nanoparticles. This review provides an overview of the methods most commonly utilized during the preclinical testing of liposomes, nanoemulsions, solid lipid nanoparticles and nanostructured lipid carriers intended for the treatment of various CNS disorders via the parenteral route. In order to fully elucidate the structure, stability, safety profiles, biodistribution, metabolism, pharmacokinetics and immunological effects of such lipid-based nanoparticles, a transdisciplinary approach to preclinical characterization is mandatory, covering a comprehensive set of physical, chemical, in vitro and in vivo biological testing.
组合化学的当代趋势以及针对脑部疾病的药物设计倾向于开发亲脂性增加且水溶性较差的候选药物，以期改善其通过血脑屏障（BBB）的递送。创新辅料/配体的日益丰富使得改善脑靶向和控制药物释放成为可能，这使得脂质纳米载体成为克服阻碍药物通过血脑屏障递送的因素的合理选择。然而，文献中使用的各种方法、研究设计和实验条件阻碍了它们的系统比较，从而减缓了基于脂质的纳米颗粒在脑靶向方面的进展。本综述概述了脂质体、纳米乳剂、固体脂质纳米颗粒和纳米结构脂质载体在临床前测试中最常用的方法，这些载体旨在通过非肠道途径治疗各种中枢神经系统疾病。为了全面阐明此类基于脂质的纳米颗粒的结构、稳定性、安全性、生物分布、代谢、药代动力学和免疫效应，必须采用跨学科方法进行临床前表征，涵盖一整套物理、化学、体外和体内生物学测试。
