Sequential release of drugs form a dual-delivery system based on pH-responsive nanofibrous mats towards wound care

Abstract

Using Chitosan/PEO as the shell and PCL as the core, chitosan–polyethylene oxide/polycaprolactone nanofibrous mats were prepared successfully by coaxial electrospinning for co-load and sequential co-delivery of two drugs. Herein, lidocaine hydrochloride (Lid), used for pain relief, was added to the shell, and curcumin (Cur), an anti-inflammatory agent, was introduced into the core. Sodium bicarbonate (SB) was also added to the core layer to provide wound microenvironment sensitivity. Under acidic conditions, Lid was released due to the formation of –NH₃⁺ by protonation of –NH₂ on the chitosan molecular chains. At the same time, SB reacted with hydrogen ions to generate CO₂, and many holes were generated on the surface of the fibers, providing more discharge paths for Cur release. Additionally, both Lid in the shell layer and Cur in the core layer exhibited acidic pH (∼5.4)-responsive release profiles. Moreover, a rapid release of Lid and a sustained release of Cur were observed to provide the immediate effects of analgesia and long-term antibacterial activity in the process of wound healing. Furthermore, after 48 h incubation, the mats showed continuous and excellent antibacterial performance against E. coli and S. aureus. The results of blood coagulation showed that the mats could achieve rapid hemostasis in the early stage of wound formation. Hemolytic and cytotoxicity evaluation also revealed that the mats had excellent hemocompatibility and cytocompatibility. Therefore, this study has made invaluable contributions to the design of a dual-drug-loaded dressing with microenvironment-responsive and sequential release properties towards wound care.