Rational Design of Rapidly Separating Dissolving Microneedles for Precise Drug Delivery by Balancing the Mechanical Performance and Disintegration Rate.

The precise delivery of traditional dissolving microneedles (TDMNs) is often limited by the incomplete insertion due to the skin deformation, and the topical irritation is inevitable after long application, which ultimately results in compromised therapeutic efficacy. The aim of this study is to develop a rapidly separating dissolving microneedles (RSDMNs) system to achieve precise drug delivery. Therapeutic molecules are concentrated in the needle tip, while the blank separating part allows it to counteract skin indentation and rapidly separate from the base part. For rational design of an ideal separating part, and the molecular interactions between polymer and sugar are explored to make a good balance between mechanical performance and disintegration rate. The optimal RSDMNs can rapidly disintegrate in the mimic skin within 30 s, and the generated micropores in the skin reseal quickly. The ex vivo drug permeation of RSDMNs is significantly higher than that of TDMNs due to the complete needle imbed aided by the separating part. Furthermore, RSDMNs exhibit excellent in vivo anti-inflammation effect by remarkably down regulating the expression of TNF-α, IL-1β, and IL-6. In conclusion, the RSDMNs can reach precise drug delivery in a short time, which are more reliable for the self-administration strategy in the future.