Long Luoxin, Zhang Chen, Hu Hong, Zhou Xinjin, Wang Yuji, Mao Lindsey F, Song Gengshen, Li Shiyou, Mao Shanhong
School of Biomedical Engineering, Capital Medical University, Beijing, 100069, China.
School of Light Industry and Engineering, Beijing Technology and Business University, Beijing, 100048, China.
Drug Deliv Transl Res. 2025 Jun 18. doi: 10.1007/s13346-025-01901-0.
Extravascular injection represents the predominant modality for contemporary drug administration. Needle injection (NI), a 180-year-old technology, provides a low-cost and effective method for delivering small-molecule drugs. However, it often results in low bioavailability for biomacromolecular drugs. Recently, needle-free jet injection (NFJI) technology has shown promise in enhancing bioavailability by promoting greater drug dispersion at delivery. However, application of the technology in clinical settings impeded by its limitations in tunability and controllability of the initial dispersion. To better understand drug dispersion at delivery, Initial Dispersion Rate (IDR) as a quantitative metric was introduced in this work. Computational Fluid Dynamics (CFD), alongside an in vitro nanosponge-gel model, were employed to investigate the correlation between IDR and various fluid properties and injection parameters. The impact of IDR on pharmacokinetics of biomacromolecular drugs was revealed in the study. Guided by a comprehensive study of IDR, a novel micro-needle jet injection (MNJI) technology was developed. In vivo animal studies demonstrated that MNJI could achieve superior injection efficiency and controllable dispersion compared to NFJI and NI. Furthermore, modifying MNJI configurations enabled tunable IDR, thereby achieving desired bioavailability for biomacromolecular drugs. To the best of our knowledge, IDR was introduced for the first time as a quantitative metric to evaluate extravascular injection efficiency, while MNJI was the first extravascular drug delivery technology that could achieve controllable and tunable dispersion at delivery.
血管外注射是当代药物给药的主要方式。针头注射（NI）作为一项已有180年历史的技术，为小分子药物的递送提供了一种低成本且有效的方法。然而，对于生物大分子药物，它往往导致生物利用度较低。最近，无针喷射注射（NFJI）技术在通过促进给药时药物更广泛分散来提高生物利用度方面显示出前景。然而，该技术在临床环境中的应用受到其初始分散的可调性和可控性方面的限制。为了更好地理解给药时的药物分散情况，本研究引入初始分散速率（IDR）作为一种定量指标。采用计算流体动力学（CFD）以及体外纳米海绵 - 凝胶模型，来研究IDR与各种流体性质和注射参数之间的相关性。该研究揭示了IDR对生物大分子药物药代动力学的影响。在对IDR进行全面研究的指导下，开发了一种新型微针喷射注射（MNJI）技术。体内动物研究表明，与NFJI和NI相比，MNJI能够实现更高的注射效率和可控的分散。此外，修改MNJI配置可实现可调的IDR，从而为生物大分子药物实现所需的生物利用度。据我们所知，IDR首次作为一种定量指标被引入以评估血管外注射效率，而MNJI是第一种能够在给药时实现可控和可调分散的血管外药物递送技术。
