Preparation and evaluation of a soluble microneedle loaded with resveratrol nanocrystals

Resveratrol (Res) has a variety of pharmacological activities, but it has not been widely used in clinical practice due to its poor water solubility and low bioavailability. Therefore, improving the solubility and utilization of Res is a key factor in increasing its clinical application. Microneedles (MNs) are a new type of transdermal drug delivery system, which has been widely noticed for its advantages of avoiding hepatic first-pass effect, reducing gastrointestinal side effects, and improving patient compliance. In recent years, the integration of nanomedicine with MNs has also become a novel therapy for drug delivery. In this study, a novel transdermal drug delivery system (Res NC MNs) was obtained by altering the crystalline form of resveratrol by media milling method, preparing resveratrol nanocrystals (Res NC), and loading Res NC into soluble microneedles prepared from sodium hyaluronate. Methods: Res NC was prepared by media milling method, and the experimental conditions, such as the type of stabilizer, the ratio of stabilizer to the drug, the number of milling beads, and the milling time, were screened to determine the optimal preparation process, using the particle size and dispersion of nanocrystals as indicators sodium hyaluronate. Dissolvable microneedles were prepared by vacuum casting method and loaded with Res NC, and then the morphology, skin puncture performance, and skin dissolution performance of Res NC MNs were examined. Results: From the in vitro release experiments, it can be seen that the resveratrol nanocrystals prepared using the optimal process had a small particle size of about 110 nm, good stability, and good release characteristics. The Res NC MNs had a good morphology, a full and uniform tip, and good skin-piercing properties and dermal solubilization properties. The Res NC MNs prepared in this study improved the drawbacks of poor water solubility and low bioavailability of resveratrol APIs, and combined with MNs, overcame the inherent defects of the traditional drug delivery methods such as oral and injection, which provided a novel idea for the integration of nanomedicine and transdermal drug delivery system.