Cui Tianyu, Li Xiuping, He Suyun, Xu Danhan, Yin Li, Huang Xiaoling, Deng Siwei, Yue Wanqing, Zhong Wenying
Department of Chemistry, Key Laboratory of Biomedical Functional Materials, School of Sciences, China Pharmaceutical University, Nanjing 211198, People's Republic of China.
Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, China Pharmaceutical University, Nanjing 211198, People's Republic of China.
ACS Biomater Sci Eng. 2020 Sep 14;6(9):5001-5011. doi: 10.1021/acsbiomaterials.0c00581. Epub 2020 Aug 13.
Infected wounds caused by persistent inflammation exhibit poor vascularization and cellular infiltration. In order to rapidly control the inflammatory effect and accelerate wound healing, it is necessary to develop a novel drug vehicle addressing the need for infected wounds. Herein, we developed a novel dual-drug delivery system with micrometer-scale alginate fibers encapsulated in instant self-assembly peptide hydrogel. Short peptides with the sequence of Nap-Gly-Phe-Phe-Lys-His (Nap-GFFKH) could self-assemble outside the microfluidic-based alginate microfibers in weak acidic solution (pH ≈ 6.0) within 5 s. The gelation condition is close to the pH environment of the human skin. We further constructed recombinant bovine basic fibroblast growth factor (FGF-2) in fibrous alginate, which was encapsulated in antibiotic-loaded peptide hydrogel. The dual-drug delivery system exhibited good mechanical property and sustained release profiles, where antibiotic could be rapidly released from the peptide hydrogel, while the growth factor could be gradually released within 7 days. Both antibacterial experiments and animal experiments confirmed that such a dual-drug delivery system has good antibacterial activity and enhances wound healing property. We suggested that the dual-drug delivery system could be potentially applied for controlled drug release in infected wound healing, drug combination for melanoma therapy, and tissue engineering.
由持续性炎症引起的感染伤口表现出血管化不良和细胞浸润不足。为了快速控制炎症反应并加速伤口愈合，有必要开发一种满足感染伤口需求的新型药物载体。在此，我们开发了一种新型双药递送系统，该系统由包裹在即时自组装肽水凝胶中的微米级海藻酸盐纤维组成。序列为Nap-Gly-Phe-Phe-Lys-His（Nap-GFFKH）的短肽可在弱酸性溶液（pH≈6.0）中于5秒内在基于微流控的海藻酸盐微纤维外自组装。凝胶化条件接近人体皮肤的pH环境。我们进一步在纤维状海藻酸盐中构建了重组牛碱性成纤维细胞生长因子（FGF-2），其被包裹在载有抗生素的肽水凝胶中。该双药递送系统表现出良好的机械性能和缓释特性，其中抗生素可从肽水凝胶中快速释放，而生长因子可在7天内逐渐释放。抗菌实验和动物实验均证实，这种双药递送系统具有良好的抗菌活性并能增强伤口愈合性能。我们认为该双药递送系统在感染伤口愈合的控释给药、黑色素瘤治疗的联合用药以及组织工程中具有潜在应用价值。
