1. General introduction 14 the aforementioned limitations conventional needle injections are far from optimal. Therefore, several energy-based devices have been developed which can increase the skin bioavailability of the administered drug, including ablative (fractional) lasers, microneedles, microdermabrasion, iontophoresis, electroporation, sonophoresis and needlefree jet injectors.33,34 Needle-free jet injectors Needle-free jet injectors (NFI) are devices that are used for non-invasive drug delivery.35 These devices operate by a high-velocity jet (between 100-200m/s) which punctures the skin and thereby enables delivery of therapeutics in the epidermis, dermis, subcutis or muscle.36,37 A conventional NFI consists of 3 key components: (1) a nozzle, (2) an injection chamber which holds the drug, and (3) a pressure source that generates a high-velocity jet.38 The pressure required to generate these high-velocity jets can be generated by a compressed gas such as CO2 or N2, or Lorentz- or piezoelectric actuators.36 The drug absorption and the injection-related pain of jet-injections is greatly influenced by the distribution pattern and penetration depth.39 How a therapeutic is distributed is affected by several characters, including the physical drug properties (influenced by the density, viscosity and formulation of the fluid), jet velocity (influenced by pressure, filling volume, stand-off distance and nozzle diameter), and skin characteristics (influenced by elasticity, epidermis thickness, porosity, density and hardness).36 NFI can overcome several limitations that conventional hypodermic needles are faced with. They can minimize treatment-related pain, are free of risk for needle stick injuries and cross-contamination, and can be an alternative treatment option for patients experiencing needle phobia. Moreover, in a previous ex-vivo study with normal skin it was shown that NFI offers a more even distribution of fluids in the skin compared to hypodermic needles.29
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