Vazula Bekkers

3. Biodistribution of needle-injections and needle-free jet-injections visualized by a 3D- Fluorescent Imaging Cryomicrotome System 75 3. INTRODUCTION Keloids are fibroproliferative scars caused by chronic inflammation in the reticular dermis. Keloids may cause pain, pruritus, movement restriction, and cosmetic concerns.1,2 They can be challenging to treat. Intralesional corticosteroid administration (ICA) by needle injection is traditionally considered a first-line treatment for keloids, with triamcinolone acetonide (TCA) being used most frequently.3,4 Nevertheless, clinical results of this treatment are highly variable and often suboptimal.5,6 Treatment efficacy can be influenced by various factors, such as the duration, size, anatomic location, genetic predisposition and treatment history of keloids.7 Additionally, treatment efficacy is influenced by drug biodistribution, which may depend on characteristics of the tissue that is injected.8,9 Drug biodistribution may also depend on the drug delivery technique. Conventional needle injection using hypodermic needles has been used predominantly for ICA in the past few decades. Yet, a wide variation in this injection technique exists in current clinical practice.4 Alternatively, different types of jet injectors can be used for ICA. Electronic pneumatic jet injectors, referred to hereinafter as ‘jet injectors’, are needle-free injectors that use pressured gasses (e.g. air or CO2) to create a high velocity jet stream of liquid drugs that penetrates the skin without using a needle.10 The drug volume and gas pressure can be adjusted to match the dose and depth of drug administration to the specific clinical requirements. To date, the biodistribution of TCA administered with different drug delivery techniques has not been investigated in different tissues. Variation in TCA biodistribution may be a major reason for the variable treatment effects of TCA in keloids reported in clinical trials and observed in clinical practice. The aim of this exploratory study is to assess the biodistribution of TCA in ex vivo keloids and normal skin with different drug delivery techniques.

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