Needle-free delivery of macromolecules across the skin by nanoliter-volume pulsed microjets

Abstract

Needle-free liquid jet injectors were invented >50 years ago for the delivery of proteins and vaccines. Despite their long history, needle-free liquid jet injectors are not commonly used as a result of frequent pain and bruising. We hypothesized that pain and bruising originate from the deep penetration of the jets and can potentially be addressed by minimizing the penetration depth of jets into the skin. However, current jet injectors are not designed to maintain shallow dermal penetration depths. Using a new strategy of jet injection, pulsed microjets, we report on delivery of protein drugs into the skin without deep penetration. The high velocity (v >100 m/s) of microjets allows their entry into the skin, whereas the small jet diameters (50 -100 m) and extremely small volumes (2-15 nanoliters) limit the penetration depth (Ϸ200 m).In vitro experiments confirmed quantitative delivery of molecules into human skin and in vivo experiments with rats confirmed the ability of pulsed microjets to deliver therapeutic doses of insulin across the skin. Pulsed microjet injectors could be used to deliver drugs for local as well as systemic applications without using needles.MEMS ͉ nanotechnology ͉ noninvasive ͉ piezoelectric ͉ transdermal

Anchoring Junctions As Drug Targets: Role in Contraceptive Development

“…This recent methodology can be used to painlessly deliver a relatively small volume of drug (usually 0.2-1 ml) within a few hundredths of a second either subcutaneously, intramuscularly, or intradermally (Baxter and Mitragotri, 2006;Arora et al, 2007). More importantly, needle-free injection offers more reliable depth of penetration and more efficient use of the drug, thereby requiring the use of significantly less drug and lowering costs.…”

Depth-controlled laser-induced jet injection for direct three-dimensional liquid delivery

“…Similarly, the geometry of micro-injections shown in the imaging cross-sections of Fig. 3a, with a thin injected column of ink capped with a larger volume on the gelatin surface, differs from the usual puncture and dispersion profile of existing needle-free microjet injectors [9,10,13]. This difference might result from the stiffer injected materials used in these previous studies, whose stiffness tend to disperse sideways the injections.…”

“…Such microjet injectors were designed to run in a repetitive [9,10] way through piezo-actuation, and studies demonstrated that this approach allows volumes with a dose precision in the nanoliter range (2-30 nL) to be delivered. Doses could further be injected locally at a frequency larger than 1 Hz within an area > 100 μm in diameter, which we define as the lateral resolution of injection.…”

“…Another approach to reduce injection-associated pain consists in producing thinner jets (50-100 μm) that penetrate in shallower skin's layers (100-200 μm) [9,10], which is sufficiently deep to cross the greatest barrier to drug transport but shallow enough to avoid the most innervated layers [11]. Such microjet injectors were designed to run in a repetitive [9,10] way through piezo-actuation, and studies demonstrated that this approach allows volumes with a dose precision in the nanoliter range (2-30 nL) to be delivered.…”

A Voice Coil Powered Controllable Micro-Jet Injection System

“…In addition to springs and compressed air, alternative driving forces have been explored in order to transform the one-time jet injection into an intermittent micro-jet injection. The micro-jet injection system was first proposed by Arora, et al [2]. It applied a piezoelectric stack actuator as the driving power.…”