Lidocaine hydrochloride loaded isomaltulose microneedles for efficient local anesthesia of the skin

Lidocaine hydrochloride (LIDH) as an anesthetic is widely used in local anesthesia. Dissolving microneedles (MNs) have great application value in the field of skin anesthesia. However, the limited drug-loading of dissolving MNs is an existing challenge that affects clinical use. In this study, we have screened isomaltulose (ISO) as the proper matrix material for the MNs by using molecular dynamics (MD) simulation. Our findings indicate that ISO has good compatibility with LIDH, and the LIDH-loaded ISO MNs (LI-MNs) have high drug-loading capacity. The drug-loading capacity of LI-MNs could reach 80%, and it could effectively puncture the skin. In addition, the preparation method of customized LI-MNs was established based on three-dimensional (3D) printing technology. It was shown that the administration time of LI-MNs could be controlled within 3 min. Also, the LI-MNs were able to provide the local anesthetic efficacy within 2 min and sustained for more than 2 h. Significantly, LI-MNs had more efficient drug efficacy compared to the topical creams and the majority of existing LIDH-loaded dissolving MNs. They even provided a longer duration of action than the injections. Overall, the LI-MNs with high drug-loading have a promising application prospect.