Intradermal Delivery of an Immunomodulator for Basal Cell Carcinoma; Expanding the Mechanistic Insight into Solid Microneedle-Enhanced Delivery of Hydrophobic Molecules.

Basal cell carcinoma (BCC) is the most common cutaneous malignancy in humans. One of the most efficacious drugs used in the management of BCC is the immunomodulator, imiquimod. However, imiquimod has physiochemical properties that limit its permeation to reach deeper, nodular tumor lesions. The use of microneedles may overcome such limitations and promote intradermal drug delivery. The current work evaluates the effectiveness of using an oscillating microneedle device Dermapen either as a pre- or post-treatment with 5% w/w imiquimod cream application to deliver the drug into the dermis. The effectiveness of microneedles to enhance the permeation of imiquimod was evaluated ex vivo using a Franz cell setup. After a 24-h permeation experiment, sequential tape strips and vertical cross-sections of the porcine skin were collected and analyzed using time-of-flight secondary ion mass spectrometry (ToF-SIMS). In addition, respective Franz cell components were analyzed using high-performance liquid chromatography (HPLC). Analysis of porcine skin cross-sections demonstrated limited dermal permeation of 5% w/w imiquimod cream. Similarly, limited dermal permeation was also seen when 5% w/w imiquimod cream was applied to the skin that was pretreated with the Dermapen, this is known as poke-and-patch. In contrast, when the formulation was applied first to the skin prior to Dermapen application, this is known as patch-and-poke, we observed a significant increase in intradermal permeation of imiquimod. Such enhancement occurs immediately upon microneedle application, generating an intradermal depot that persists for up to 24 h. Intradermal colocalization of isostearic acid, an excipient in the cream, with imiquimod within microneedle channels was also demonstrated. However, such enhancement in intradermal delivery of imiquimod was not observed when the patch-and-poke strategy was used with a non-oscillating microneedle applicator, the Dermastamp. The current work highlights that using the patch-and-poke approach with an oscillating microneedle pen may be a viable approach to improve the current treatment in BCC patients who would prefer a less invasive intervention relative to surgery.