Optimized use of a biodegradable polymer as a carrier material for the local delivery of recombinant human bone morphogenetic protein-2 (rhBMP-2)
Optimized use of a biodegradable polymer as a carrier material for the local delivery of recombinant human bone morphogenetic protein-2 (rhBMP-2)
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DOI：
10.1016/j.biomaterials.2005.10.007
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发表时间：
2006-03-01
期刊：
影响因子：
14
通讯作者：
Takaoka, K
中科院分区：
文献类型：
--
作者：
Kato, M;Toyoda, H;Takaoka, K
为了提高聚D，L-乳酸与聚乙二醇嵌段共聚物（PLA-DX-PEG）作为重组人骨形态发生蛋白（rhBMP）药物释放系统的有效性，在小鼠异位成骨模型中，我们研究了PLA-DX-PEG的体积、rhBMP-2的剂量与骨诱导的关系，在一系列研究中，我们比较了PLA-DX-PEG和载有不同量rhBMP（0、1、2、5、10、20 μ g）的胶原海绵异位诱导的骨的大小和骨矿物质含量（BMC）。另一个实验被设计来研究PLA-DX-PEG聚合物体积的范围（15，30，60，90毫克）与固定的rhBMP浓度（0.01重量%），如何改变的大小和BMC的诱导听小骨。聚合物体积的影响也在进一步的实验中进行了检查，其中将固定量的rhBMP置于一定范围的PLA-DX-PEG共聚物体积中，以得到每个植入物不同浓度的蛋白质结果表明，骨产率线性依赖于rhBMP的剂量，并且还与高于rhBMP的最小浓度的聚合物体积成比例。2（在该系列中为0.0017重量%）。rhBMP-2在PLA-DX-PEG中的最佳浓度为0.003wt%。这些数据为植入物的制造提供了重要的见解，这些植入物使用最低可能剂量的这种昂贵的骨诱导蛋白来提供rhBMP-2的有效递送。这些信息将对BMP的临床应用有价值。(C)2005爱思唯尔有限公司保留所有权利。
To improve the efficacy of a block copolymer of poly-D, L-lactic acid with randomly inserted p-dioxanone and polyethylene glycol (PLA-DX-PEG) as a drug delivery system for recombinant human bone morphogerietic proteins (rhBMPs),. we examined the relationship between the volume of PLA-DX-PEG, the dose of rhBMP-2 and osteoinduction in a mouse model of ectopic bone formation.In a series of studies, we compared the size and bone mineral content (BMC) of ectopically induced bone by PLA-DX-PEG and colla en sponges carrying different quantities of rhBMP (0, 1, 2, 5, 10, 20 mu g). An additional experiment was designed to investigate how range of PLA-DX-PEG polymer volumes (15, 30, 60 90 mg) with a fixed rhBMP concentration (0.01 wt%), altered the size and BMC of the induced ossicle. The influence of polymer volume was also examined in a further experiment wherein a fixed amount of rhBMP was placed in a range of PLA-DX-PEG copolymer volumes to give different concentrations of the protein per implant (0.02-0.0017 wt%).The results indicate that the bone yields were linearly dependent on the dose of rhBMP and also were proportional to the polymer volume above the minimal concentration of rhBMP-2 (0.0017 wt% in this series). The optimal concentration of rhBMP-2 in PLA-DX-PEG was 0.003 wt% in mice. The data provide important insights into the fabrication of implants that provide efficacious delivery of rhBMP-2 using the lowest possible dose of this expensive osteoinductive protein. This information will be of value for the clinical use of BMPs. (C) 2005 Elsevier Ltd. All rights reserved.