Brako Francis, Boateng Joshua
School of Science, Faculty of Engineering and Science, University of Greenwich, Chatham, Maritime, UK.
Expert Opin Drug Deliv. 2025 Apr;22(4):525-553. doi: 10.1080/17425247.2025.2470224. Epub 2025 Feb 25.
Traditional administration routes have limitations including first-pass metabolism and gastrointestinal degradation for sensitive drugs (oral) and pain associated with parenteral injections, which also require trained personnel and refrigeration, making them expensive. This has increased interest in alternative routes, with mucosal surfaces being of high priority.
Mucosal routes include ocular, oral (buccal/sublingual), nasal and vaginal mucosae which avoid the limitations of the oral and parenteral routes. Though mucosal routes show great potential, they are still hindered by several barriers, especially for systemic absorption, resulting in the development of more advanced novel drug delivery systems to overcome these limitations and achieve therapeutic actions both locally and systemically, similar to or exceeding the oral route. This paper systematically reviews and compares the different mucosal routes, challenges, and recent advances in advanced novel drug delivery system design for emerging clinical challenges including the advent of large biological macromolecules (proteins, peptides, and RNA) for treatment and prevention of diseases. The review also focuses on current challenges and future perspectives.
Among the various transmucosal routes discussed, nose-to-brain drug delivery has the greatest translational potential to go beyond the current state of the art and achieve significant clinical impact for neurological diseases.
传统给药途径存在局限性,对于敏感药物而言,口服给药存在首过代谢和胃肠道降解问题,而注射给药会带来疼痛,且需要专业人员操作和冷藏保存,成本较高。这使得人们对替代给药途径的兴趣增加,其中黏膜表面给药成为重点关注对象。
黏膜给药途径包括眼部、口腔(颊部/舌下)、鼻腔和阴道黏膜给药,这些途径可避免口服和注射给药途径的局限性。尽管黏膜给药途径具有巨大潜力,但仍受到多种屏障的阻碍,尤其是在全身吸收方面,因此需要开发更先进的新型药物递送系统来克服这些局限性,实现局部和全身的治疗效果,达到或超越口服给药的效果。本文系统回顾并比较了不同的黏膜给药途径、面临的挑战以及针对包括用于疾病治疗和预防的大型生物大分子(蛋白质、肽和RNA)出现等新出现的临床挑战在先进新型药物递送系统设计方面的最新进展。该综述还关注了当前的挑战和未来展望。
在所讨论的各种经黏膜给药途径中,鼻脑给药在突破现有技术水平并对神经疾病产生重大临床影响方面具有最大的转化潜力。