RESUMEN
Chronic pain emerges as a major global health issue, significantly impacting individuals' health and quality of life. In this study, we designed a bilayer microneedle loaded with lidocaine nanocomposites in the inner layer and adrenaline (Adr) in the outer layer (HCP MNs) for modulated sequential release to achieve prolonged local anesthesia. The obtained HCP MNs featured an intact structure with adequate mechanical strength for efficient skin penetration. The bilayer structure of MNs was evidenced by loading two fluorescent dyes in each layer. Furthermore, these HCP MNs were capable of inducing rapid as well as prolonged local anesthetic effects in guinea pigs. Hence, the bilayer MN coloaded with Adr and lidocaine nanocomposite serves as a promising transdermal delivery platform for chronic pain management.