Kumar Siddhant, Yadav Akshay, Verma Rahul K, Kumar Akhilesh, Gupta Piyush Kumar, Shukla Rahul
Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER-Raebareli), Lucknow, Uttar Pradesh 226002, India.
Pharmaceutical Nanotechnology Lab, Institute of Nano Science and Technology (INST), Sector-81, Mohali, Punjab 160062, India.
Mol Pharm. 2025 Jul 7;22(7):3602-3620. doi: 10.1021/acs.molpharmaceut.5c00386. Epub 2025 Jun 23.
Neurodegenerative diseases have always posed a significant therapeutic challenge due to the restrictive nature of the blood-brain barrier (BBB). Intranasal drug delivery has emerged as a noninvasive approach to bypass the BBB, enabling targeted brain drug delivery while improving drug retention and transport. This review explores the physiological basis of the nose-to-brain pathway and various formulation strategies including mucoadhesive systems, permeation enhancers, and magnetophoretic approaches. Additionally, strategies to enhance intranasal delivery, such as P-glycoprotein inhibitors, cell-penetrating peptides, and enzyme inhibitors, are discussed alongside nanotechnology-based carriers, including surface-modified and bioconjugated systems. The role of specialized intranasal drug delivery devices (e.g., ViaNase, Optimist, and SipNose) in enhancing precision dosing is also highlighted. Despite its promise, intranasal delivery faces challenges such as limited therapeutic windows, scalability issues, and the constraint of the nasal cavity volume, which can accommodate only 200 μL of liquid per nostril. Optimizing drug stability, achieving accurate dosing, and enhancing bioavailability without nasal irritation remain key hurdles. Future research should focus on the development of commercially feasible nanoformulations and innovative medical devices to improve drug targeting and treatment efficacy for patients with neurodegenerative diseases.
由于血脑屏障（BBB）的限制特性，神经退行性疾病一直构成重大的治疗挑战。鼻内给药已成为一种绕过血脑屏障的非侵入性方法，能够实现靶向脑内给药，同时提高药物滞留和转运。本综述探讨了鼻脑途径的生理基础以及各种制剂策略，包括粘膜粘附系统、渗透促进剂和磁泳方法。此外，还讨论了增强鼻内给药的策略，如P-糖蛋白抑制剂、细胞穿透肽和酶抑制剂，以及基于纳米技术的载体，包括表面修饰和生物共轭系统。还强调了专门的鼻内给药装置（如ViaNase、Optimist和SipNose）在提高精准给药方面的作用。尽管鼻内给药前景广阔，但仍面临诸如治疗窗有限、可扩展性问题以及鼻腔容积限制（每个鼻孔仅能容纳200 μL液体）等挑战。优化药物稳定性、实现精确给药以及在无鼻腔刺激的情况下提高生物利用度仍然是关键障碍。未来的研究应侧重于开发商业上可行的纳米制剂和创新医疗设备，以改善神经退行性疾病患者的药物靶向性和治疗效果。
