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基于红细胞的药物载体工程:蛋白质释放和生物活性的控制。

Engineering of erythrocyte-based drug carriers: control of protein release and bioactivity.

机构信息

School of Materials Science and Engineering, Nanyang Technological University, Singapore, Singapore.

出版信息

J Mater Sci Mater Med. 2012 Jan;23(1):63-71. doi: 10.1007/s10856-011-4485-2. Epub 2011 Nov 18.

Abstract

This work reports the fabrication of layer-by-layer (LbL) polyelectrolyte coated erythrocyte carriers that provide a simple means for controlling the burst and subsequent release of lysozyme. Erythrocytes were loaded with RITC-lysozyme as model compound via the hypotonic dialysis method. An encapsulation efficiency of 41.6% and a loading amount of 12.7 pg/cell was achieved. It is demonstrated that these carriers maintain their shape and integrity similar to natural erythrocytes after the encapsulation procedures, and achieve a uniform distribution of the encapsulated lysozyme. The erythrocyte carriers were fixed with glutaraldehyde and then successfully coated with biocompatible polyelectrolytes, poly-L: -lysine hydrobromide and dextran sulfate, using the LbL method. It is demonstrated that the release profile of the encapsulated macromolecule can be regulated by adjusting the number of polyelectrolyte layers. Furthermore by adjusting the concentrations of the cross linking agent the activity of the encapsulated lysozyme can be well preserved. These core-shell microcapsules, consisting of erythrocytes loaded with bioactive substances and coated with a polyelectrolyte multilayer shell, hold promise for a new type of biocompatible and biodegradable drug delivery system.

摘要

本工作报道了层层(LbL)聚电解质包覆红细胞载体的制备,为控制溶菌酶的突释和随后的释放提供了一种简单的方法。通过低渗透析法将 RITC-溶菌酶加载到红细胞中作为模型化合物。实现了 41.6%的包封效率和 12.7pg/细胞的载药量。研究表明,这些载体在包封过程后保持其类似于天然红细胞的形状和完整性,并实现了包封溶菌酶的均匀分布。用戊二醛固定红细胞载体,然后使用 LbL 法成功地用生物相容性聚电解质、聚-L:-赖氨酸氢溴酸盐和硫酸葡聚糖进行包覆。研究表明,通过调整聚电解质层数可以调节包封大分子的释放曲线。此外,通过调整交联剂的浓度可以很好地保持包封溶菌酶的活性。这些由负载生物活性物质的红细胞和包被聚电解质多层壳组成的核壳微胶囊有望成为新型的生物相容性和可生物降解的药物传递系统。

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