Acute postoperative pain is commonly treated with Flurbiprofen (FBP), but conventional delivery methods are suboptimal. This study prepared a new non-burst release microneedles (MNs) using genipin cross-linked gelatin (cGel). By adding varying amounts of genipin to modulate the crosslinking degree of cGel, the drug release behavior of the drug-loaded MNs in the skin can be altered. The crosslinking parameters that meet therapeutic requirements are selected, thus providing rapid and long-lasting analgesic effects. cGel solutions were successfully cross-linked, altering matrix material microstructure, confirmed by scanning electron microscope imaging and fourier transform infrared spectroscopy. MNs demonstrated increasing mechanical strength with higher crosslinking. Drug release rates were rapid initially, then slowed, exhibiting a characteristic of decreased release rates with increasing degrees of crosslinking. In vivo, FBP/cGel MNs significantly reduced allodynia and hyperalgesia post-surgery, with the greatest effect observed at 2-3 hours post-surgery, and can maintain analgesia for up to 6 hours. Biosafety tests confirmed good biocompatibility. FBP/cGel MNs effectively penetrate the stratum corneum, safely delivering drugs with significant analgesic effects, excellent mechanical properties and good biocompatibility, representing a promising strategy for managing acute postoperative pain.

In cutaneous cosmetology surgery, local injection or coated anesthetics are generally used to provide analgesia at the treatment site to achieve painless operation. Due to the barrier of corneum, topical cream may cause uncertain dosage and delayed analgesia. Local injection has problems such as pain, infection, and misoperation. Therefore, it is necessary to develop a painless and rapid administration method for local anesthesia. Here, a lidocaine/hyaluronic acid bubble microneedle patch (Lido/HA bMNP) was prepared for rapid drug delivery and efficient analgesia. The bubble structure between microneedles (MNs) and the backing layer allowed the MNs to efficiently penetrate into the skin and remove from the backing layer under shear force to rapidly complete the administration. Drugs were quickly released with the dissolution of HA within 15 s, which immediately played an analgesic effect and lasted for 1 h. Lido/HA bMNP could deliver precise doses to the skin in an extremely short time, which had the advantages of convenient operation, high biosafety, rapid onset of analgesia, and reasonable pain relief time. This patch provided an alternative way for local anesthesia and it was a promising transdermal drug delivery method for the realization of high quality and efficiency “painless medical beauty”.