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PLGA 分散体的温敏胶凝:向可注射胶体细胞递药系统发展。

Thermally-triggered gelation of PLGA dispersions: towards an injectable colloidal cell delivery system.

机构信息

Biomaterial Science Group, School of Materials, The University of Manchester, Grosvenor Street, Manchester M17HS, UK.

出版信息

J Colloid Interface Sci. 2010 Apr 1;344(1):61-9. doi: 10.1016/j.jcis.2009.12.030. Epub 2009 Dec 22.

DOI:10.1016/j.jcis.2009.12.030
PMID:20070971
Abstract

In this study the properties of poly(D,L-lactide-co-glycolide) (PLGA) dispersions containing a thermoresponsive cationic copolymer were investigated. The PLGA dispersions were prepared by interfacial deposition in aqueous solution and were rendered thermoresponsive by addition of a cationic poly(N-isopropyl acrylamide) (PNIPAm) graft copolymer. The copolymers used had the general composition PDMA(x)(+)-g-(PNIPAm(n))(y). DMA(+) is quarternarized N,N-dimethylaminoethyl methacrylate. The PDMA(x)(+)-g-(PNIPAm(n))(y) copolymers have x and y values that originate from the macroinitiator used for their preparation; values for n correspond to the PNIPAm arm length. The thermoresponsive dispersions were characterised using photon correlation spectroscopy, turbidity measurements and electrophoretic mobility measurements. A strong electrostatic attraction between the anionic PLGA particles and cationic copolymer was present and the dispersions showed thermally-triggered gelation at total polymer volume fractions as low as 0.015. These new PLGA gels, which formed at about 32 degrees C, had elastic modulus values that could be controlled using dispersion composition. Scanning electron micrographs of the gels showed high porosity and interconnectivity of elongated pores. Remarkably, the gels were flexible and had critical yield strains as high as 160%. The ability of the gels to support growth of bovine nucleus pulposus cells was investigated using two-dimensional cell culture. The cells proliferated and remained viable on the gels after 3days. The results suggest that this general family of biodegradable thermogelling PLGA dispersions, introduced here for the first time, may have longer-term application as an injectable colloidal cell delivery system.

摘要

在这项研究中,研究了含有温敏阳离子共聚物的聚(D,L-丙交酯-共-乙交酯)(PLGA)分散体的性质。PLGA 分散体通过在水溶液中的界面沉积制备,并通过添加温敏阳离子聚(N-异丙基丙烯酰胺)(PNIPAm)接枝共聚物使其具有温敏性。所用的共聚物具有一般组成 PDMA(x)(+)-g-(PNIPAm(n))(y)。DMA(+) 是季铵化的 N,N-二甲基氨基乙基甲基丙烯酸酯。PDMA(x)(+)-g-(PNIPAm(n))(y)共聚物的 x 和 y 值源自用于其制备的大分子引发剂;n 值对应于 PNIPAm 臂的长度。使用光子相关光谱法、浊度测量法和电泳迁移率测量法对温敏分散体进行了表征。带负电荷的 PLGA 粒子与阳离子共聚物之间存在强静电吸引力,分散体在总聚合物体积分数低至 0.015 时表现出热触发凝胶化。这些新的 PLGA 凝胶在约 32°C 形成,其弹性模量值可以通过分散体组成来控制。凝胶的扫描电子显微镜照片显示出高孔隙率和伸长孔的互连性。值得注意的是,凝胶具有柔韧性,临界屈服应变高达 160%。使用二维细胞培养研究了凝胶对牛髓核细胞生长的支持能力。细胞在凝胶上增殖并在 3 天后保持存活。结果表明,这种新引入的通用可生物降解温敏凝胶 PLGA 分散体家族可能具有作为可注射胶体细胞递送系统的长期应用前景。

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