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 micronee-dles(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 isomal-tulose(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 promis-ing application prospect.