Institut für Technische Chemie, Technische Universität Braunschweig, Hagenring 30, 38106 Braunschweig, Germany.
Helmholtz-Zentrum für Infektionsforschung, Inhoffenstrasse 10, 38124 Braunschweig, Germany.
Biomolecules. 2018 Sep 28;8(4):103. doi: 10.3390/biom8040103.
Nanoparticles can be used as a smart drug delivery system, when they release the drug only upon degradation by specific enzymes. A method to create such responsive materials is the formation of hydrogel nanoparticles, which have enzymatically degradable crosslinkers. Such hydrogel nanoparticles were prepared by ionotropic gelation sodium alginate with lysine-rich peptide sequences-either α-poly-L-lysine (PLL) or the aggrecanase-labile sequence KKKK-GRD-ARGSV↓NITEGE-DRG-KKKK. The nanoparticle suspensions obtained were analyzed by means of dynamic light scattering and nanoparticle tracking analysis. Degradation experiments carried out with the nanoparticles in suspension revealed enzyme-induced lability. Drugs present in the polymer solution during the ionotropic gelation can be encapsulated in the nanoparticles. Drug loading was investigated for interferon-β (IFN-β) as a model, using a bioluminescence assay with MX2Luc2 cells. The encapsulation efficiency for IFN-β was found to be approximately 25%. The nanoparticles suspension can be used to spray-coat titanium alloys (Ti-6Al-4V) as a common implant material. The coatings were proven by ellipsometry, reflection-absorption infrared spectroscopy, and X-ray photoelectron spectroscopy. An enzyme-responsive decrease in layer thickness is observed due to the degradation of the coatings. The Alg/peptide coatings were cytocompatible for human gingival fibroblasts (HGFIB), which was investigated by CellTiterBlue and lactate dehydrogenase (LDH) assay. However, HGFIBs showed poor adhesion and proliferation on the Alg/peptide coatings, but these could be improved by modification of the alginate with a RGD-peptide sequence. The smart drug release system presented can be further tailored to have the right release kinetics and cell adhesion properties.
纳米粒子可用作智能药物输送系统，只有在特定酶降解时才会释放药物。一种制造这种响应性材料的方法是形成水凝胶纳米粒子，其具有可酶降解的交联剂。通过离子凝胶作用将具有富含赖氨酸的肽序列的海藻酸钠制备成这种水凝胶纳米粒子，这些肽序列要么是α-聚-L-赖氨酸（PLL），要么是 aggrecanase 不稳定序列 KKKK-GRD-ARGSV↓NITEGE-DRG-KKKK。通过动态光散射和纳米颗粒跟踪分析对获得的纳米颗粒悬浮液进行分析。在悬浮液中进行的纳米颗粒降解实验表明酶诱导的不稳定性。在离子凝胶化过程中存在于聚合物溶液中的药物可以被封装在纳米颗粒中。使用 MX2Luc2 细胞的生物发光测定法研究了干扰素-β（IFN-β）作为模型的药物包封，发现 IFN-β 的包封效率约为 25%。纳米颗粒悬浮液可用于喷涂钛合金（Ti-6Al-4V）作为常见植入物材料。通过椭偏仪、反射吸收红外光谱和 X 射线光电子能谱证明了涂层的存在。由于涂层的降解，观察到酶响应性的层厚度降低。Alg/肽涂层对人牙龈成纤维细胞（HGFIB）具有细胞相容性，通过 CellTiterBlue 和乳酸脱氢酶（LDH）测定法进行了研究。然而，HGFIB 在 Alg/肽涂层上的粘附和增殖能力较差，但通过 RGD-肽序列对藻酸盐进行修饰可以改善这些情况。所提出的智能药物释放系统可以进一步定制，以具有合适的释放动力学和细胞粘附特性。
