Microneedle penetration and injection past the stratum corneum in humans

Background/objective: Solid and hollow microneedles hold potential for painless vaccinations and drug injections. Hollow microneedles offer the potential for short-term bolus injections and long-term continuous injections. However, efficient injection requires complete penetration through the lipophilic stratum corneum. Furthermore, human skin is elastic, making microneedle penetration challenging. Here, we investigate whether hollow microneedles can penetrate and inject past the stratum corneum in human volunteers. Methods: Hexyl nicotinate (HN) induces skin capillary vasodilation and was used as the marker of stratum corneum penetration because of its lipophilic nature and slow partition from the lipophilic stratum corneum to the hydrophilic epidermis. We compared topical application of HN with microneedle injection at tape-stripped and unstripped sites on the volar forearms of five humans. Results: Microneedle injections decreased the time to reach maximum cutaneous blood flow by threefold, regardless of whether the stratum corneum had or had not been tape-stripped (p < 0.05). Conclusion: Our results demonstrate that hollow microneedle arrays deliver past the stratum corneum and not into the stratum corneum. Therefore, microneedles improve delivery in humans by penetrating past the stratum corneum and would be especially useful in the delivery of lipophilic drugs that partition slowly from the stratum corneum into the epidermis.