Biocompatibility of elastin-like polymer poly(VPAVG) microparticles:: in vitro and in vivo studies
Biocompatibility of elastin-like polymer poly(VPAVG) microparticles:: in vitro and in vivo studies
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DOI：
10.1002/jbm.a.30702
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发表时间：
2006-08-01
影响因子：
4.9
通讯作者：
Herrero-Vanrell, R.
中科院分区：
文献类型：
--
作者：
Rincon, A. C.;Molina-Martinez, I. T.;Herrero-Vanrell, R.
Poly(L-valine-L-proline-L-alanine-L-valine-L-glycine)(VPAVG)是一种属于弹性蛋白样家族的新型蛋白质聚合物。这些聚合物是基于某些短肽单体的重复出现，这些单体被认为是天然弹性蛋白中的“积木”。这种智能的热响应性聚合物能够在生理温度下自结合，在水中形成约60%的聚集体。这种能力可以用来制备负载有活性物质的微粒。本报告的目的是从实验结果评估由聚(VPAVG)制备的微粒的生物相容性。我们研究了微粒的细胞毒性作用、大鼠(n=6)皮下注射(1 mg和2.5 mg)后的水肿形成以及玻璃体内注射2.5 mg聚(VPAVG)微粒后的眼内耐受性(n=12)。在本研究所研究的聚合物浓度范围内(20、30、40和60 mg/mL)，该聚合物对巨噬细胞没有任何细胞毒性或非特异性的细胞呼吸抑制作用。大鼠后爪皮下注射微粒后，未见炎症反应，对照组与实验组之间无显著差异。在眼内注射聚(VPAVG)微粒后，评估眼前节和后节的体征。注射后第28天，实验组仅有少数眼(2/11)出现炎症征象。然而，45%(5/11)接受微粒的眼出现牵引性视网膜脱离。本工作观察到的结果表明，眼内注射聚(VPAVG)微粒后具有一定的成纤维细胞活性。(C)2006年威利期刊公司。
Poly(L-valine-L-proline-L-alanine-L-valine-L-glycine) (VPAVG) is a new kind of proteinaceous polymer belonging to the Elastin-like family. These polymers are based on the recurrence of certain short peptide monomers that are considered as "building blocks" in the natural elastin. This smart thermoresponsive polymer has the ability to self-associate at physiological temperature to form aggregates with about 60% in water. This ability can be harnessed to prepare microparticles loaded with an active substance. The aim of this report is to evaluate, from the results of the experiment conducted, the biocompatibility of microparticles prepared from poly(VPAVG). We have studied the cytotoxic effects of microparticles, edema formation after subcutaneous injection (1 and 2.5 mg) in rats (n = 6), and also intraocular tolerance after the intravitreal injection of 2.5 mg of poly(VPAVG) microparticles into pigmented rabbits (n = 12). The polymer did not induce any cytotoxicity or nonspecific depression of cellular respiration on macrophages under the range of polymer concentrations investigated in this study (20, 30, 40, and 60 mg/mL). We observed no inflammatory response to microparticles after subcutaneous injection in the hind-paw of rats, with no significant differences between the control group (PBS) and experimental groups. Anterior and posterior segment signs were evaluated after intraocular injection of poly(VPAVG) microparticles. Only a few eyes (2/11) of the experimental group presented inflammation signs at day 28 postinjection. Nevertheless, 45% (5/11) of the eyes receiving microparticles showed tractional retinal detachment. The results observed in this work suggested certain fibroblastic activity induced by poly(VPAVG) microparticles after their intraocular injection. (c) 2006 Wiley Periodicals, Inc.