School & Hospital of Stomatology, Wenzhou Medical University, Wenzhou, People's Republic of China.
Department of Stomatology, PLA Strategic Support Force Medical Center, Beijing, People's Republic of China.
Int J Nanomedicine. 2023 Mar 31;18:1725-1740. doi: 10.2147/IJN.S401705. eCollection 2023.
Much attention has been paid to sustained drug release and anti-infection in wound management. Hydrogels, which are biocompatible materials, are promising tools for controlled drug release and infective protection during wound healing. However, hydrogels also demonstrate limitations in the highly efficient treatment of wounds because of the diffusion rate. In this work, we explored pH-sensitive hydrogels that enable ultra-long-acting drug release and sustained antibacterial properties.
We constructed a hybrid gelatin methacrylate (GelMA) system with sustainable antibacterial properties combining hyaluronic acid (HA)-coated mesoporous silica nanoparticles (MSN), which loaded host-guest complexes of chlorhexidine (CHX) with β-cyclodextrins (β-CD) (CHX⊂CD-MSN@HA@GelMA). The release mechanism of CHX was explored using UV-vis spectra after intermittent diffusion of CHX. The hybrid hydrogels were characterized, and the drug content in terms of the release profile, bacterial inhibition, and in vivo experiments were investigated.
Except for dual protection from both hydrogels, MSN in the HA improved the drug loading efficiency to promote the local drug concentration. It showed that complicated CHX-loaded MSN releases CHX more gradually and over a longer duration than CHX-loaded MSNs. This demonstrated a 12-day CHX release time and antibacterial activity, primarily attributable to the capacity of β-CD to form an inclusion complex with CHX. Meanwhile, in vivo experiments revealed that the hydrogels safely promote skin wound healing and enhance therapeutic efficacy.
We constructed pH-sensitive CHX⊂CD-MSN@HA@GelMA hydrogels that enable ultra-long-acting drug release and sustained antibacterial properties. The combination of β-CD and MSN would be better suited to release a reduced rate of active molecules over time (slow delivery), making them great candidates for wound dressing anti-infection materials.
在伤口管理中，人们非常关注药物的持续释放和抗感染作用。水凝胶作为一种生物相容性材料，是控制药物释放和感染保护的有前途的工具，可促进伤口愈合。然而，由于扩散速率的限制，水凝胶在高效治疗伤口方面也存在局限性。在这项工作中，我们探索了 pH 敏感水凝胶，使其具有超长效药物释放和持续抗菌性能。
我们构建了一种具有可持续抗菌性能的混合明胶甲基丙烯酸酯（GelMA）系统，该系统结合了负载有主客体配合物氯己定（CHX）与β-环糊精（β-CD）的透明质酸（HA）包覆介孔硅纳米粒子（MSN）（CHX⊂CD-MSN@HA@GelMA）。通过间歇扩散 CHX 后的紫外可见光谱研究了 CHX 的释放机制。对混合水凝胶进行了表征，并对药物含量、释放曲线、抑菌作用和体内实验进行了研究。
除了水凝胶的双重保护外，HA 中的 MSN 提高了药物负载效率，以促进局部药物浓度。结果表明，负载 CHX 的 MSN 比负载 CHX 的 MSN 更能缓慢、持续地释放 CHX。这表明 CHX 的释放时间和抗菌活性长达 12 天，主要归因于β-CD 与 CHX 形成包合物的能力。同时，体内实验表明，水凝胶能安全促进皮肤伤口愈合，增强治疗效果。
我们构建了 pH 敏感的 CHX⊂CD-MSN@HA@GelMA 水凝胶，使其具有超长效药物释放和持续抗菌性能。β-CD 和 MSN 的结合将更适合随着时间的推移以较低的速率释放活性分子（缓慢传递），使它们成为伤口敷料抗感染材料的理想选择。
