Key Laboratory of Biomaterials of Guangdong Higher Education Institutes, Department of Biomedical Engineering, Jinan University, Guangzhou, 510632, China; Nanhai Longtime Pharmaceutical Co Ltd, Foshan, Guangzhou, 510632, China.
Department of Pharmacy, Wenzhou Hospital of Integrated Traditional Chinese and Western Medicine, Wenzhou, Zhejiang, China.
Colloids Surf B Biointerfaces. 2018 Dec 1;172:573-585. doi: 10.1016/j.colsurfb.2018.09.006. Epub 2018 Sep 5.
Excessive deposition of extracellular matrix (ECM) usually resulted in scar formation during wound healing, which caused skin dysfunction, such as hair loss. Basic fibroblast growth factor (bFGF) was very helpful for promoting hair follicle neogenesis and regulating the remodeling of ECM during wound healing. Because of its poor stability in wound fluids and low permeability against the dense wound scar, the repairing quality of bFGF on wound was hindered largely in clinical practice. To overcome these drawbacks, herein, a novel liposome with silk fibroin hydrogel core (bFGF-SF-LIP) was firstly prepared to stabilize bFGF, followed by insertion of laurocapam, a permeation enhancer, into the liposomal membrane to construct a skin-permeable liposome (SP-bFGF-SF-LIP). The encapsulated efficiency of bFGF was reaching to nearly 90% when ratio of drug/lipids above 1:300, and it activity was not compromised by laurocapam. SP-bFGF-SF-LIP exhibited a hydrodynamic diameter of 103.3 nm and Zeta potential of -2.31 mV. The stability of the encapsulated bFGF in wound fluid was obviously enhanced. After 24 h of incubation with wound fluid containing MMP-9, the remaining bFGF was as high as 65.4 ± 0.5% for SP-bFGF-SF-LIP, while only 2.1 ± 0.2% of free bFGF was remained. The skin-permeability of bFGF was significantly enhanced by SP-bFGF-SF-LIP and most of the encapsulated bFGF penetrated into the dermis. After treatment with SP-bFGF-SF-LIP, the morphology of hair follicle at wound zone was obviously improved and the hair regrew on the deep second scald mice model. The therapeutic mechanism was highly associated with inhibiting scar formation and promoting vascular growth in dermis. Conclusively, SP-bFGF-SF-LIP may a potential option to improve wound healing with high-quality.
细胞外基质(ECM)的过度沉积通常会导致伤口愈合时形成疤痕,从而导致皮肤功能障碍,如脱发。碱性成纤维细胞生长因子(bFGF)在促进毛囊新生和调节伤口愈合过程中 ECM 的重塑方面非常有帮助。由于其在伤口液中的稳定性差,并且对致密的伤口疤痕的渗透性低,因此 bFGF 在临床上对伤口的修复质量受到很大限制。为了克服这些缺点,本文首次制备了一种具有丝素蛋白水凝胶核的新型脂质体(bFGF-SF-LIP),以稳定 bFGF,然后将渗透增强剂月桂氮卓酮插入脂质体膜中,构建一种皮肤渗透性脂质体(SP-bFGF-SF-LIP)。当药物/脂质比高于 1:300 时,bFGF 的包封效率接近 90%,并且其活性不受月桂氮卓酮的影响。SP-bFGF-SF-LIP 的水动力学直径为 103.3nm,Zeta 电位为-2.31mV。包封的 bFGF 在伤口液中的稳定性明显增强。在含有 MMP-9 的伤口液中孵育 24 小时后,SP-bFGF-SF-LIP 中仍有高达 65.4±0.5%的 bFGF 残留,而游离 bFGF 仅残留 2.1±0.2%。SP-bFGF-SF-LIP 显著增强了 bFGF 的皮肤渗透性,大部分包封的 bFGF 渗透到真皮中。用 SP-bFGF-SF-LIP 处理后,伤口区域的毛囊形态明显改善,深度二度烫伤小鼠模型上的毛发重新生长。治疗机制与抑制疤痕形成和促进真皮血管生长密切相关。总之,SP-bFGF-SF-LIP 可能是改善高质量伤口愈合的一种有潜力的选择。