Zhang Pei, Liu Chenguang
College of Marine Life Sciences, Ocean University of China, Qingdao 266003, China.
Department of Life Science, Luoyang Normal University, Luoyang 471934, China.
Polymers (Basel). 2020 Jul 20;12(7):1612. doi: 10.3390/polym12071612.
The self-assembly of hydrophobically modified polymers has become a research hotspot due to its wide application in the biomedical field. Recombinant human epidermal growth factors (rhEGFs) are molecules that are able to enhance wound healing; however, they have a short half-life and require sustained action to enhance their mitogenic effect on epithelial cells. Here, we proposed a new delivery system to avoid the inhibition of rhEGF by various enzymes, thus improving its bioavailability and sustained release. The amphiphilic polymer was composed of conjugated linoleic acid (CLA) and carboxymethyl chitosan (CMCS), which were further characterized by fourier transformed infrared spectroscopy (FTIR) and H nuclear magnetic resonance (H NMR). Then, the self-assembly behavior of CLA-CMCS (CC) polymer in water was observed in which the particle size of CC decreased from 196 to 155 nm with the degree of CLA substitution increasing. The nanoparticles were loaded with rhEGF and the maximum rhEGF loading efficiency (LE) of CC3 nanoparticles was 82.43 ± 3.14%. Furthermore, CC nanoparticles (NPs) exhibited no cytotoxicity for L929 cells, and cell proliferation activity was well preserved after rhEGF loading to CC-NPs and was comparable to that of free rhEGF. Topically applied rhEGF:CC-NPs significantly accelerated the wound-closure rate in full thickness, which was most probably due to its sustained release and enhanced skin permeation. In conclusion, carboxymethyl chitosan-based nanoparticles were constructed and showed good cytocompatibility. Moreover, these findings also demonstrated the therapeutic potential of rhEGF:CC-NPs as a topical wound-healing drug carrier.
由于疏水改性聚合物在生物医学领域的广泛应用，其自组装已成为研究热点。重组人表皮生长因子（rhEGF）是能够促进伤口愈合的分子；然而，它们的半衰期较短，需要持续作用以增强其对上皮细胞的促有丝分裂作用。在此，我们提出了一种新的递送系统，以避免rhEGF被各种酶抑制，从而提高其生物利用度和缓释性能。两亲性聚合物由共轭亚油酸（CLA）和羧甲基壳聚糖（CMCS）组成，通过傅里叶变换红外光谱（FTIR）和氢核磁共振（H NMR）对其进行了进一步表征。然后，观察了CLA-CMCS（CC）聚合物在水中的自组装行为，其中随着CLA取代度的增加，CC的粒径从196 nm减小到155 nm。纳米颗粒负载了rhEGF，CC3纳米颗粒的最大rhEGF负载效率（LE）为82.43±3.14%。此外，CC纳米颗粒（NPs）对L929细胞无细胞毒性，rhEGF负载到CC-NPs后细胞增殖活性得到良好保留，与游离rhEGF相当。局部应用rhEGF:CC-NPs显著加快了全层伤口的闭合速度，这很可能是由于其缓释和增强的皮肤渗透性所致。总之，构建了基于羧甲基壳聚糖的纳米颗粒，其表现出良好的细胞相容性。此外，这些发现还证明了rhEGF:CC-NPs作为局部伤口愈合药物载体的治疗潜力。
