104(11):4255-60. Epub 2007 Mar 6.

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

Biomolecular Science and Engineering, University of California, Santa Barbara, CA 93106, USA.

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 mum) and extremely small volumes (2-15 nanoliters) limit the penetration depth ( approximately 200 mum). 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.

PMID: 17360511 [PubMed - indexed for MEDLINE]PMCID: PMC1838589 

150(3):455-61.

Assessment of the biological performance of the needle-free injector INJEX using the isolated porcine forelimb.

Vitro-Tec Entwicklungs-GmbH, Wiesenweg 10, D-12247 Berlin, Germany. wagner@vitro-tec.de

Abstract

BACKGROUND: The development and utilization of novel needle-free injection devices in order to minimize needle stick injuries make increasing demands for suitable assay systems, which reflect the physiological situation in humans as close as possible.

OBJECTIVES: It was therefore the goal of the present study to test the biological performance of a needle-free injector (INJEX) by the use of porcine skin as a model with a high predictive value for the feasibility in humans because of its close similarity to human skin.

METHODS: In order to use porcine skin in the context of the underlying tissues, the isolated porcine forelimb was chosen as an assay model for use with the INJEX injector. Ink or the fluorescent dye fluorescein-isothiocyanate was injected and the penetration depth was determined metrically and dye distribution histologically. To assess the resorption of heparin, needle injection was compared with needle-free injection in a perfused limb model.

RESULTS: Increasing amounts of ink increasingly penetrated into subcutaneous tissue layers in a cone-shaped manner mainly following lead structures. Penetration was hampered by skin thickness and by the deep muscle fascia, which served as a penetration barrier. Resorption of heparin was similar irrespective of injection by the use of a needle or the INJEX device.

CONCLUSIONS: The isolated porcine forelimb serves as a versatile tool for the assessment of the biological performance of needle-free injection devices such as INJEX. Further studies are necessary to correlate the model for drug delivery in humans.

PMID: 15030327 [PubMed - indexed for MEDLINE