Gomes Mariana, Ramalho Maria João, Loureiro Joana A, Pereira Maria Carmo
LEPABE-Laboratory for Process Engineering, Environment, Biotechnology and Energy, Faculty of Engineering, University of Porto, Rua Dr. Roberto Frias, 4200-465 Porto, Portugal.
ALiCE-Associate Laboratory in Chemical Engineering, Faculty of Engineering, University of Porto, Rua Dr. Roberto Frias, 4200-465 Porto, Portugal.
Pharmaceutics. 2025 May 17;17(5):661. doi: 10.3390/pharmaceutics17050661.
: The blood-brain barrier (BBB) poses a major obstacle to delivering therapeutic agents to the central nervous system (CNS), driving the need for innovative drug delivery strategies. Among these, nanoparticles (NPs) have gained attention due to their ability to enhance drug transport, improve bioavailability, and enable targeted delivery. : This paper explores various surface modification strategies employed to optimize NP-mediated drug delivery across the BBB. Specifically, the functionalization of NPs with ligands such as transferrin (Tf), lactoferrin (Lf), protamine, and insulin is discussed, each demonstrating unique mechanisms for enhancing brain-targeting efficiency. In addition, this work provides a comprehensive overview of recent scientific advancements and market strategies aimed at accelerating the adoption of low-cost, surface-modified nanoparticles, ultimately improving patient access to effective CNS treatments. : Preclinical and in vitro studies have demonstrated the effectiveness of these modifications in increasing drug retention and bioavailability in brain tissues. Additionally, while ligand-conjugated NPs hold significant promise for neuropharmacology, their clinical translation is often hindered by regulatory and economic constraints. Lengthy approval processes can slow market entry, but cost-benefit analyses indicate that surface-modified NPs remain financially viable, particularly as scalable manufacturing techniques and some ligands are cost-efficient.
血脑屏障（BBB）对将治疗药物输送到中枢神经系统（CNS）构成了重大障碍，这推动了对创新药物递送策略的需求。在这些策略中，纳米颗粒（NPs）因其能够增强药物运输、提高生物利用度并实现靶向递送而受到关注。
本文探讨了为优化纳米颗粒介导的跨血脑屏障药物递送而采用的各种表面修饰策略。具体而言，讨论了用转铁蛋白（Tf）、乳铁蛋白（Lf）、鱼精蛋白和胰岛素等配体对纳米颗粒进行功能化，每种配体都展示了增强脑靶向效率的独特机制。此外，这项工作全面概述了旨在加速采用低成本、表面修饰纳米颗粒的最新科学进展和市场策略，最终改善患者获得有效中枢神经系统治疗的机会。
临床前和体外研究已经证明了这些修饰在增加脑组织中药物滞留和生物利用度方面的有效性。此外，虽然配体偶联的纳米颗粒在神经药理学方面具有巨大潜力，但其临床转化往往受到监管和经济限制的阻碍。漫长的审批过程会减缓市场进入速度，但成本效益分析表明，表面修饰的纳米颗粒在经济上仍然可行，特别是随着可扩展的制造技术和一些配体具有成本效益。
