Overcoming barriers: nanomedicine-based strategies for nose-to-brain delivery

For therapeutics to reach the brain, the several administration routes available come with some disadvantages, with the primary biological obstacle being the blood-brain barrier (BBB), which is not easy to penetrate despite the sophisticated technologies which have been developed. In addition, reaching specific brain structures invokes additional challenges, entailing more complicated delivery strategies. Nose-to-brain (N2B) delivery or the intranasal (IN) administration route provides a less invasive alternative. With the wealth of knowledge available on N2B delivery of nanomedicines and biotherapeutics, there is an opportunity to synthesize the current literature, especially in terms of promising strategies to improve N2B delivery of nanomedicines, highlighting experimental evaluation and translational challenges. We also emphasized the latest advancements in experimental models for nasal delivery. Aiming to bridge the gap between bench research and clinical application, we reviewed the cases of insulin and oxytocin, two biotherapeutics with high clinical potential for CNS-related diseases, and explore how nanomedicine-based platforms can enhance their effectiveness. This review offers a roadmap for overcoming barriers and accelerating the clinical translation of N2B therapeutics.