I3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal; INEB - Instituto de Engenharia Biomédica, Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal; ICBAS - Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal; CESPU - Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde, Rua Central de Gandra 1317, 4585-116 Gandra, Portugal.
I3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal; INEB - Instituto de Engenharia Biomédica, Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal; CESPU - Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde, Rua Central de Gandra 1317, 4585-116 Gandra, Portugal.
J Control Release. 2020 Jun 10;322:390-400. doi: 10.1016/j.jconrel.2020.03.042. Epub 2020 Apr 2.
The central nervous system (CNS), namely the brain, still remains as the hardest area of the human body to achieve adequate concentration levels of most drugs, mainly due to the limiting behavior of its physical and biological defenses. Lipid nanocapsules emerge as a versatile platform to tackle those barriers, and efficiently delivery different drug payloads due to their numerous advantages. They can be produced in a fast, solvent-free and scalable-up process, and their properties can be fine-tuned for to make an optimal brain drug delivery vehicle. Moreover, lipid nanocapsule surface modification can further improve their bioavailability towards the central nervous system. Coupling these features with alternative delivery methods that stem to disrupt or fully circumvent the blood-brain barrier may fully harness the therapeutic advance that lipid nanocapsules can supply to current treatment options. Thus, this review intends to critically address the development of lipid nanocapsules, as well as to highlight the key features that can be modulated to ameliorate their properties towards the central nervous system delivery, mainly through intravenous methods, and how the pathological microenvironment of the CNS can be taken advantage of. The different routes to promote drug delivery towards the brain parenchyma are also discussed, as well as the synergetic effect that can be obtained by combining modified lipid nanocapsules with new/smart administration routes.
中枢神经系统（CNS），即大脑，仍然是人体中最难达到大多数药物充分浓度的区域，主要是由于其物理和生物防御的限制行为。脂质纳米胶囊作为一种通用平台，可以克服这些障碍，并由于其众多优势有效地输送不同的药物有效载荷。它们可以在快速、无溶剂和可扩展的过程中生产，并且可以对其性质进行微调，以制成最佳的脑内药物输送载体。此外，脂质纳米胶囊表面修饰可以进一步提高其向中枢神经系统的生物利用度。将这些特性与旨在破坏或完全绕过血脑屏障的替代输送方法相结合，可能会充分利用脂质纳米胶囊为当前治疗选择提供的治疗进展。因此，本综述旨在批判性地探讨脂质纳米胶囊的发展，并强调可以调节的关键特性，以改善其向中枢神经系统输送的特性，主要是通过静脉内方法，以及如何利用中枢神经系统病理微环境。还讨论了促进药物向脑实质输送的不同途径，以及通过将修饰的脂质纳米胶囊与新的/智能给药途径相结合可以获得的协同效应。
