Choi Sang Won, Oak Min-Ho, Yi Eunyoung, Kim Hyun Jung, Park Jin Woo
College of Pharmacy and Natural Medicine Research Institute, Mokpo National University, Muan-gun, Jeonnam 58554, Republic of Korea.
J Nanosci Nanotechnol. 2018 Feb 1;18(2):887-892. doi: 10.1166/jnn.2018.14863.
Percutaneous delivery of growth factors is often used to treat wounds, and for cosmetic purposes, as a way of accelerating healing and skin regeneration, respectively. However, the therapeutic effects of growth factors are diminished by their poor absorption when delivered percutaneously, in addition to their rapid degradation by proteinases. To overcome these obstacles, we constructed two skin-permeable compounds. Basic fibroblast growth factor (bFGF) and vascular endothelial growth factor-A (VEGF-A) were both genetically paired with low-molecular-weight protamine (LMWP), to yield the compounds LMWP-bFGF and LMWP-VEGF-A, respectively. The molecular weights and N-terminal amino acid sequences of LMWP-bFGF and LMWP-VEGF-A confirmed that the N-terminus-specific conjugation of LMWP with bFGF and VEGF-A had been successful. The biological abilities of the native factors to stimulate human fibroblast (CCD-986sk) and endothelial cell proliferation were preserved. Both compounds significantly promoted wound (scratch) recovery and enhanced procollagen type I C-peptide synthesis in CCD-986sk cells (to levels 184 and 133% those of the native compounds, respectively). The LMWP-conjugated growth factors were significantly more permeable than the native forms (by 7.29- and 29.22-fold, respectively). Finally, encapsulation of the compounds in positively charged elastic nanoliposomes (115 ± 1.54 nm in diameter with a zeta potential of 57.2 ± 3.05 mV) further improved both permeation and stability. Thus, nanoliposomes loaded with LMWP-conjugated growth factors are expected to enhance skin regeneration; the materials will find applications in wound-healing therapies and anti-wrinkle cosmetics.
生长因子的经皮递送常用于治疗伤口，以及出于美容目的，分别作为加速愈合和皮肤再生的一种方式。然而，生长因子经皮递送时吸收不佳，且会被蛋白酶快速降解，从而降低了其治疗效果。为克服这些障碍，我们构建了两种可透皮的化合物。碱性成纤维细胞生长因子（bFGF）和血管内皮生长因子-A（VEGF-A）均与低分子量鱼精蛋白（LMWP）进行基因配对，分别产生化合物LMWP-bFGF和LMWP-VEGF-A。LMWP-bFGF和LMWP-VEGF-A的分子量和N端氨基酸序列证实，LMWP与bFGF和VEGF-A的N端特异性偶联是成功的。天然因子刺激人成纤维细胞（CCD-986sk）和内皮细胞增殖的生物学能力得以保留。两种化合物均显著促进伤口（划痕）恢复，并增强CCD-986sk细胞中I型前胶原C肽的合成（分别达到天然化合物水平的184%和133%）。与天然形式相比，LMWP偶联的生长因子的渗透性显著更高（分别提高了7.29倍和29.22倍）。最后，将这些化合物封装在带正电荷的弹性纳米脂质体中（直径为115±1.54 nm，ζ电位为57.2±3.05 mV），进一步提高了渗透性和稳定性。因此，负载LMWP偶联生长因子的纳米脂质体有望促进皮肤再生；这些材料将在伤口愈合疗法和抗皱化妆品中得到应用。
