Department of Chemistry, University of Rochester, Rochester, NY 14627-0216, USA.
J Mater Chem B. 2020 Aug 5;8(30):6366-6377. doi: 10.1039/d0tb01157f.
Supramolecular hydrogels have great potential as biomaterials for sustained delivery of therapeutics. While peptide-based supramolecular hydrogels have been developed that show promise for drug delivery applications, the high cost of production has limited their widespread adoption. Low molecular weight (LMW) supramolecular hydrogels are emerging as attractive and inexpensive alternatives to peptide-based hydrogels. We recently reported novel cationic fluorenylmethyloxycarbonyl-modified phenylalanine (Fmoc-Phe) hydrogels for localized and sustained in vivo release of an anti-inflammatory agent for functional pain remediation. In an effort to further elucidate design principles to optimize these materials for delivery of a variety of molecular agents, we herein report a systematic examination of electrostatic effects on the release of cargo molecules from Fmoc-Phe derived hydrogels. Specifically, we interrogate the release of cationic, anionic, and neutral cargo molecules from a series of cationic and anionic Fmoc-Phe derived hydrogels. We observed that cargo was readily released from the hydrogels except when the cargo and hydrogel network had complementary charges, in which case the cargo was highly retained in the network. These results demonstrate that the electrostatic characteristics of both the hydrogel network and the specific cargo are critical design parameters in the formulation of LMW supramolecular hydrogel systems in the development of next-generation materials for drug delivery applications.
超分子水凝胶作为治疗药物持续释放的生物材料具有巨大的潜力。虽然已经开发出基于肽的超分子水凝胶，显示出在药物输送应用方面的前景，但生产成本高限制了它们的广泛采用。低分子量（LMW）超分子水凝胶作为基于肽的水凝胶的有吸引力且廉价的替代品而出现。我们最近报道了新型阳离子芴甲氧羰基修饰的苯丙氨酸（Fmoc-Phe）水凝胶，用于局部和体内持续释放抗炎剂以修复功能性疼痛。为了进一步阐明设计原则，以便为各种分子药物的输送优化这些材料，我们在此系统地研究了静电效应对从 Fmoc-Phe 衍生水凝胶中释放货物分子的影响。具体来说，我们研究了一系列阳离子和阴离子 Fmoc-Phe 衍生水凝胶中阳离子、阴离子和中性货物分子的释放。我们观察到货物很容易从水凝胶中释放出来，除非货物和水凝胶网络具有互补电荷，在这种情况下，货物会高度保留在网络中。这些结果表明，水凝胶网络和特定货物的静电特性是 LMW 超分子水凝胶系统配方中的关键设计参数，对于开发用于药物输送应用的下一代材料非常重要。
