Shi Pengzhong, Luo Shan, Voit Brigitte, Appelhans Dietmar, Zan Xingjie
School of Ophthalmology and Optometry, Eye Hospital, School of Biomedical Engineering, Wenzhou Medical University, Wenzhou, Zhejiang Province 325035, P. R. China.
J Mater Chem B. 2018 Jul 7;6(25):4205-4215. doi: 10.1039/c8tb00312b. Epub 2018 Jun 13.
Basic proteins play important roles in biological activities and disease treatment, but their high sensitivity to the body environment and short life time have limited their applications. Encapsulating the proteins into carriers has been demonstrated to be an effective way to prolong the protein half life time and to control the release temporally and spatially. However, fabricating protein carriers with high protein loading efficacy under mild conditions is still a big challenge. The capsules generated by the combination of the layer by layer (LBL) technique and sacrificial templates have been extensively investigated for the encapsulation of proteins. Porous CaCO is an effective sacrificial template with the ability to load various drugs efficiently under mild conditions, but it shows very poor ability in loading basic proteins. Here, we developed a highly efficient but very simple method to encapsulate lysozyme into porous CaCO. An efficiency of 99.5% and capacity of 91.6 mg g under very gentle conditions were obtained by doping heparin into porous CaCO. Most importantly, the activity of the encapsulated lysozyme was almost 100% retained. Furthermore, we evaluated the encapsulation efficiency of the loaded lysozyme during the LBL wrapping process and demonstrated that the loss of the loaded lysozyme was controllable by choosing suitable polyelectrolyte pairs. Considering the multi-interaction mode of heparin with various proteins and the ability to retain the function of the loaded protein demonstrated in our study, we believe that the developed approach has great potential for encapsulating various functional proteins with a wide range of applications in catalysis, disease treatment, and tissue engineering.
碱性蛋白质在生物活性和疾病治疗中发挥着重要作用，但其对机体环境高度敏感且寿命较短，限制了它们的应用。已证明将蛋白质封装到载体中是延长蛋白质半衰期以及在时间和空间上控制释放的有效方法。然而，在温和条件下制备具有高蛋白负载效率的蛋白质载体仍然是一个巨大挑战。通过层层（LBL）技术与牺牲模板相结合产生的胶囊已被广泛研究用于蛋白质封装。多孔碳酸钙是一种有效的牺牲模板，能够在温和条件下高效负载各种药物，但它在负载碱性蛋白质方面表现出非常差的能力。在此，我们开发了一种高效且非常简单的方法将溶菌酶封装到多孔碳酸钙中。通过将肝素掺杂到多孔碳酸钙中，在非常温和的条件下获得了99.5%的效率和91.6 mg/g的载量。最重要的是，封装的溶菌酶活性几乎100%得以保留。此外，我们评估了在LBL包裹过程中负载溶菌酶的封装效率，并证明通过选择合适的聚电解质对，负载溶菌酶的损失是可控的。考虑到肝素与各种蛋白质的多重相互作用模式以及我们研究中所展示的保留负载蛋白质功能的能力，我们相信所开发的方法在封装各种功能蛋白质方面具有巨大潜力，这些蛋白质在催化、疾病治疗和组织工程等领域具有广泛应用。
