title: Characterization of needle-assisted jet injections.
abstract: Hypodermic injections have been the standard for transcutaneous drug delivery for many years. However, needle phobia, pain, and risks of needle-stick injuries have manifested in poor patient compliance. Needle-free jet injections (NFJI) have been developed to address these drawbacks but the reliability of dose and depth of delivery have been limited by a lack of control over jet parameters, and by variability in the skin's mechanical properties among individuals. Moreover, the device size and cost have been restrained by the high pressure (>20MPa) required to penetrate the skin. Needle-assisted jet injections have been proposed to improve delivery reliability of conventional jet injectors by penetrating the skin with a short needle (<5mm) and thereby allowing jet delivery to a desired injection depth at a reduced pressure. This study characterized needle-assisted jet injections performed after first penetrating the skin with a 1.5mm needle, examining the effect of needle size on jet parameters, and evaluating injection performance in porcine skin. A voice-coil actuated jet injector was modified to incorporate needles of 30G, 31G and 32G. A series of pulse tests was performed to compare jet velocity and injection volume across the needle sizes, where it was found that the jet velocity and injection volume achieved with 32G needles were 13% and 16% lower, respectively, than with 30G. In contrast, there was no significant difference in jet velocity and injection volume between 30G and 31G needles, suggesting that a reduction of 10μm in the mean inner diameter of the 31G needle has minimal impact on jet velocity and injection volume. Injection studies performed in porcine skin revealed that injections driven by fluid pressures ranging between 0.8MPa and 1.4MPa were able to achieve substantial injectate penetration (~10mm) and delivery (~100μL) into subcutaneous fat regardless of needle size, in a period of 40ms. The required pressures are an order of magnitude lower than those used in NFJI, yet still maintain the high-speed nature of jet injection by achieving a delivery rate of 2.25mL/s. The lower pressures required in needle-assisted drug delivery can lead to reduced device size and cost, as well as reduced shear stresses during jet injection and can therefore minimise the potentially adverse effect of shear on the structural integrity of proteins, vaccines and DNA.
authors.affiliation: Auckland Bioengineering Institute, The University of Auckland, Auckland, New Zealand. Electronic address: xli230@aucklanduni.ac.nz.
authors.forename: Xinxin
authors.initials: X
authors.lastname: Li
authors.affiliation: Auckland Bioengineering Institute, The University of Auckland, Auckland, New Zealand; Department of Engineering Science, The University of Auckland, Auckland, New Zealand. Electronic address: b.ruddy@auckland.ac.nz.
authors.forename: Bryan
authors.initials: B
authors.lastname: Ruddy
authors.affiliation: Auckland Bioengineering Institute, The University of Auckland, Auckland, New Zealand; Department of Engineering Science, The University of Auckland, Auckland, New Zealand. Electronic address: a.taberner@auckland.ac.nz.
authors.forename: Andrew
authors.initials: A
authors.lastname: Taberner
mesh_terms: D000818:Animals; D016503:Drug Delivery Systems; D004867:Equipment Design; D007277:Injections, Jet; D009339:Needles; D004364:Pharmaceutical Preparations / Q000008:administration & dosage*; D015203:Reproducibility of Results; D012867:Skin / Q000378:metabolism*; D050151:Subcutaneous Fat / Q000378:metabolism*; D013552:Swine
chemical_list: D004364:Pharmaceutical Preparations
keywords: Jet injection; Needle-assisted; Transdermal delivery; Voice coil