Spasojevic Milica, Bhujbal Swapnil, Paredes Genaro, de Haan Bart J, Schouten Arend J, de Vos Paul
Department of Polymer Chemistry, Zernike Institute for Advanced Materials, University of Groningen, 9747, AG Groningen, the Netherlands; Departments of Pathology and Laboratory Medicine, Section of Medical Biology, Division of Immunoendocrinology, University of Groningen, Hanzeplein 1, 9700, RB Groningen, The Netherlands.
J Biomed Mater Res A. 2014 Jun;102(6):1887-96. doi: 10.1002/jbm.a.34863. Epub 2013 Jul 24.
Alginate-based microcapsules are being proposed for treatment of many types of diseases. A major obstacle however in the successes is that these capsules are having large lab-to-lab variations. To make the process more reproducible, we propose to cover the surface of alginate capsules with diblock polymers that can form polymer brushes. In the present study, we describe the stepwise considerations for successful application of diblock copolymer of polyethylene glycol (PEG) and poly-L-lysine (PLL) on the surface of alginate beads. Special procedures had to be designed as alginate beads are hydrophilic and most protocols are designed for hydrophobic biomaterials. The successful attachment of diblock copolymer and the presence of PEG blocks on the surface of the capsules were studied by fluorescence microscopy. Longer time periods, that is, 30-60 min, are required to achieve saturation of the surface. The block lengths influenced the strength of the capsules. Shorter PLL blocks resulted in less stable capsules. Adequate permeability of the capsules was achieved with poly(ethylene glycol)-block-poly(L-lysine hydrochloride) (PEG454-b-PLL100) diblock copolymers. The capsules were a barrier for immunoglobulin G. The PEG454-b-PLL100 capsules have similar mechanical properties as PLL capsules. Minor immune activation of nuclear factor κB in THP-1 monocytes was observed with both PLL and PEG454-b-PLL100 capsules prepared from purified alginate. Our results show that we can successfully apply block copolymers on the surface of hydrophilic alginate beads without interfering with the physicochemical properties.
基于藻酸盐的微胶囊正被用于多种疾病的治疗。然而,成功应用的一个主要障碍是这些胶囊在不同实验室之间存在很大差异。为了使该过程更具可重复性,我们建议用能形成聚合物刷的双嵌段聚合物覆盖藻酸盐胶囊的表面。在本研究中,我们描述了将聚乙二醇(PEG)和聚-L-赖氨酸(PLL)的双嵌段共聚物成功应用于藻酸盐珠表面的逐步考量。由于藻酸盐珠是亲水性的,而大多数方案是为疏水性生物材料设计的,所以必须设计特殊程序。通过荧光显微镜研究了双嵌段共聚物的成功附着以及胶囊表面PEG嵌段的存在情况。需要更长的时间,即30 - 60分钟,才能使表面达到饱和。嵌段长度影响胶囊的强度。较短的PLL嵌段会导致胶囊稳定性较差。聚(乙二醇)-嵌段-聚(L-赖氨酸盐酸盐)(PEG454-b-PLL100)双嵌段共聚物使胶囊具有足够的渗透性。这些胶囊对免疫球蛋白G具有屏障作用。PEG454-b-PLL100胶囊与PLL胶囊具有相似的机械性能。用由纯化藻酸盐制备的PLL和PEG454-b-PLL100胶囊在THP-1单核细胞中均观察到核因子κB的轻微免疫激活。我们的结果表明,我们可以在亲水性藻酸盐珠表面成功应用嵌段共聚物,而不干扰其物理化学性质。