1. General introduction 13 1. patients’ lives. Therefore, there is a high need for new efficacious, safe and minimal invasive treatment options for patients with severe and/or recalcitrant keloids. Conventional hypodermic needles Injection with conventional hypodermic needles is among the most commonly used procedures in clinical practice, but is hampered by high procedure-related pain and cannot be used in patients with (acquired) needle-phobia.27 Previous literature shows that approximately 2 in 3 children and 1 in 4 adult patients fear needles.28 The exact cause of needle-phobia is not fully understood, but traumatic experiences associated with needles during childhood (or during treatment) may set the stage for some patients.7 Other disadvantages of conventional needle injections include a lack of standardization: volume, pressure and the depth of the injection varies and is highly operator dependent. Furthermore, the procedure related pain can significantly hamper the effectiveness of the treatment and some patients prematurely decide to discontinue treatment. In addition, conventional needle injections can technically be difficult to administer in keloids, because of the tough fibroproliferative scar tissue.29 Alternative dermal drug delivery techniques Dermal drug delivery facilitates targeting of active substances to the appropriate skin layer(s) for the treatment of dermatological diseases.30 However, the stratum corneum, the most superficial layer of the skin, plays a crucial role as the physical barrier against pathogens but also to the penetration of compounds into skin.30 Drugs can only be delivered passively via the skin if it has an adequate lipophilicity and a low molecular mass preferably <500 Da.31 Due to the physical barrier of the skin, medication containing larger drug molecules may not be absorbed via the skin at all, and therefore have no efficacy when applied topically.32 To overcome the main obstacle, the stratum corneum, drugs can be injected intradermally or intralesionally using conventional hypodermic needles. However, due to
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