Center for Biopharmaceuticals and Biobarriers in Drug Delivery (BioDelivery), Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark.
Department of Science and Environment, Roskilde University, Universitetsvej 1, DK-4000 Roskilde, Denmark.
J Colloid Interface Sci. 2024 Jun;663:449-457. doi: 10.1016/j.jcis.2024.02.101. Epub 2024 Feb 13.
Self-assembled hyaluronic acid-based nanogels are versatile drug carriers due to their biodegradable nature and gentle preparation conditions, making them particularly interesting for delivery of peptide therapeutics. This study aims to elucidate the relation between peptide structure and encapsulation in a nanogel. Key peptide properties that affect encapsulation in octenyl succinic anhydride-modified hyaluronic acid nanogels were identified as we explored the effect on nanogel characteristics using 12 peptides with varying charge and hydrophobicity. The size and surface properties of the microfluidics-assembled peptide-loaded nanogels were evaluated using dynamic light scattering, laser Doppler electrophoresis, and small angle neutron scattering. Additionally, the change in peptide secondary structure upon encapsulation in nanogels, their release from the nanogels, and the in vitro antimicrobial activity were assessed. In conclusion, the more hydrophobic peptides showed stronger binding to the nanogel carrier and localized internally rather than on the surface of the nanogel, resulting in more spherical nanogels with smoother surfaces and slower release profiles. In contrast, cationic and hydrophilic peptides localized at the nanogel surface resulting in fluffier nanogel structures and quick and more complete release in biorelevant medium. These findings emphasize that the advantages of nanogel delivery systems for different applications depend on the therapeutic peptide properties.
自组装的透明质酸纳米凝胶由于其可生物降解的性质和温和的制备条件，是多功能的药物载体，特别适合递呈肽类治疗药物。本研究旨在阐明肽结构与纳米凝胶包封之间的关系。我们通过使用 12 种具有不同电荷和疏水性的肽来探索对纳米凝胶特性的影响，确定了影响辛烯基琥珀酸酐修饰的透明质酸纳米凝胶包封的关键肽性质。使用动态光散射、激光多普勒电泳和小角中子散射评估了微流控组装的载肽纳米凝胶的粒径和表面性质。此外，还评估了肽二级结构在纳米凝胶中的变化、从纳米凝胶中的释放以及体外抗菌活性。总之，疏水性较强的肽与纳米凝胶载体的结合更强，并且定位在内部而不是纳米凝胶的表面，导致纳米凝胶具有更球形的表面和更平滑的表面，以及更慢的释放曲线。相比之下，阳离子和亲水性肽定位在纳米凝胶表面，导致纳米凝胶结构更蓬松，在生物相关介质中快速且完全释放。这些发现强调了纳米凝胶给药系统对不同应用的优势取决于治疗性肽的性质。
