Micro-needle jet injection technology for tunable drug dispersion at delivery

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.