Stie Mai Bay, Fennema Galparsoro Dirk, Zhou Xin, Foderà Vito
Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100, Copenhagen, Denmark; Center for Biopharmaceuticals and Biobarriers in Drug Delivery (BioDelivery), University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark.
Dipartimento di Fisica e Chimica, Università degli Studi di Palermo, Viale delle scienze Edificio 18, 90128 Palermo, Italy.
Eur J Pharm Sci. 2025 Jan 1;204:106962. doi: 10.1016/j.ejps.2024.106962. Epub 2024 Nov 16.
Protein self-assemblies in the form of ordered supramolecular structures such as particulates hold great potential as new biomaterials. However, research in this field is rarely conducted under physiologically relevant conditions but such studies are crucially needed to unravel the potential use of particulates and other amyloid structures in health sciences. In this study, particulates of α-lactalbumin (ALA) were prepared at different stages of maturation by thermal incubation. Disassembly of particulates in isotonic buffer, neutral pH and at 37 °C was investigated by simultaneously measuring Thioflavin T fluorescence intensity and light scattering. Freshly formed particulates quickly disassembled and displayed complete release of soluble ALA within 1 h. Mature particulates displayed slower disassembly kinetics with incomplete release of ALA within 1 h. The biocompatibility of particulates at different maturation stages to epithelial lung and fibroblast cells was assessed in vitro. Good cell compatibility was observed in the presence of the particulates and their released species. Our findings display protein particulates as biodegradable and highly tunable particles, promoting them as good candidates for drug delivery purposes.
以有序超分子结构形式存在的蛋白质自组装体，如颗粒，作为新型生物材料具有巨大潜力。然而，该领域的研究很少在生理相关条件下进行，但此类研究对于揭示颗粒和其他淀粉样结构在健康科学中的潜在用途至关重要。在本研究中，通过热孵育在不同成熟阶段制备了α-乳白蛋白（ALA）颗粒。通过同时测量硫黄素T荧光强度和光散射，研究了颗粒在等渗缓冲液、中性pH值和37°C条件下的拆解情况。新形成的颗粒迅速拆解，并在1小时内显示出可溶性ALA的完全释放。成熟颗粒的拆解动力学较慢，1小时内ALA释放不完全。体外评估了不同成熟阶段颗粒对肺上皮细胞和成纤维细胞的生物相容性。在颗粒及其释放产物存在的情况下观察到良好的细胞相容性。我们的研究结果表明蛋白质颗粒是可生物降解且高度可调的颗粒，使其成为药物递送目的的良好候选者。
