Wanselius Marcus, Rodler Agnes, Searle Sean S, Abrahmsén-Alami Susanna, Hansson Per
Department of Medicinal Chemistry, Uppsala University, SE-751 23 Uppsala, Sweden.
Innovation Strategies & External Liaison, Pharmaceutical Technology & Development, Operations, AstraZeneca, SE-431 83 Gothenburg, Sweden.
Gels. 2022 Sep 15;8(9):588. doi: 10.3390/gels8090588.
Volume changes of responsive microgels can probe interactions between polyelectrolytes and species of opposite charges such as peptides and proteins. We have investigated a microfluidics method to synthesize highly responsive, covalently crosslinked, hyaluronic acid microgels for such purposes. Sodium hyaluronate (HA), pre-modified with ethylacrylamide functionalities, was crosslinked in aqueous droplets created with a microfluidic technique. We varied the microgel properties by changing the degree of modification and concentration of HA in the reaction mixture. The degree of modification was determined by H NMR. Light microscopy was used to investigate the responsiveness of the microgels to osmotic stress in aqueous saline solutions by simultaneously monitoring individual microgel species in hydrodynamic traps. The permeability of the microgels to FITC-dextrans of molecular weights between 4 and 250 kDa was investigated using confocal laser scanning microscopy. The results show that the microgels were spherical with diameters between 100 and 500 µm and the responsivity tunable by changing the degree of modification and the HA concentration. Microgels were fully permeable to all investigated FITC-dextran probes. The partitioning to the microgel from an aqueous solution decreased with the increasing molecular weight of the probe, which is in qualitative agreement with theories of homogeneous gel networks.
响应性微凝胶的体积变化能够探测聚电解质与带相反电荷的物质（如肽和蛋白质）之间的相互作用。为了实现此目的，我们研究了一种微流控方法来合成具有高响应性、共价交联的透明质酸微凝胶。用乙基丙烯酰胺官能团预先改性的透明质酸钠（HA）在通过微流控技术产生的水滴中进行交联。我们通过改变反应混合物中HA的改性程度和浓度来改变微凝胶的性质。改性程度通过核磁共振氢谱（¹H NMR）测定。利用光学显微镜，通过同时监测流体动力学陷阱中的单个微凝胶种类，研究微凝胶在盐水溶液中对渗透压的响应性。使用共聚焦激光扫描显微镜研究微凝胶对分子量在4至250 kDa之间的异硫氰酸荧光素标记葡聚糖（FITC - dextrans）的渗透性。结果表明，微凝胶呈球形，直径在100至500 µm之间，其响应性可通过改变改性程度和HA浓度进行调节。微凝胶对所有研究的FITC - 葡聚糖探针完全可渗透。从水溶液到微凝胶的分配随着探针分子量的增加而降低，这与均相凝胶网络理论在定性上是一致的。
