Wang Guilin, Siggers Kevin, Zhang Sufeng, Jiang Hongxing, Xu Zhenghe, Zernicke Ronald F, Matyas John, Uludağ Hasan
Department of Chemical and Materials Engineering, Faculty of Engineering, University of Alberta, Edmonton, Alberta, Canada.
Pharm Res. 2008 Dec;25(12):2896-909. doi: 10.1007/s11095-008-9692-2. Epub 2008 Aug 15.
The purpose of this study was to investigate the preparation process of bone morphogenetic protein-2 (BMP-2) containing bovine serum albumin (BSA) nanoparticles (NPs), and to assess the bioactivity of BMP-2 encapsulated in such NPs.
The NPs were prepared by a coacervation method, and the effects of process parameters on NP size and polydispersity were examined. Polymer coated NPs were characterized with respect to amount of adsorbed polymer, particle size and zeta potential. Using bone marrow stromal cells (BMSC), biocompatibility of the NPs was investigated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) Assay, and bioactivity of the encapsulated BMP-2 was investigated by alkaline phosphatase (ALP) induction and calcification.
The size of NPs could be controlled in the 50-400 nm range by process parameters including BSA concentration, non-solvent:solvent ratio and pH value. After coating with cationic polymers, the particle size and zeta potential were significantly increased. MTT assay indicated no toxicity of both the uncoated and coated NPs on BMSC. Based on ALP induction and calcification, full retention of BMP-2 bioactivity was retained in the polymer-coated NPs.
This study described a preparation procedure for BSA NPs with controllable particle size, and such polymer-coated BSA NPs are promising delivery agents for local and systemic administration of BMP-2 in bone regeneration.
本研究旨在探究含骨形态发生蛋白-2(BMP-2)的牛血清白蛋白(BSA)纳米颗粒(NPs)的制备过程,并评估包封于此类纳米颗粒中的BMP-2的生物活性。
通过凝聚法制备纳米颗粒,研究工艺参数对纳米颗粒大小和多分散性的影响。对聚合物包被的纳米颗粒的吸附聚合物量、粒径和zeta电位进行表征。使用骨髓基质细胞(BMSC),通过3-(4,5-二甲基噻唑-2-基)-2,5-二苯基溴化四氮唑(MTT)法研究纳米颗粒的生物相容性,并通过碱性磷酸酶(ALP)诱导和钙化研究包封的BMP-2的生物活性。
通过包括BSA浓度、非溶剂与溶剂比例和pH值在内的工艺参数,可将纳米颗粒的大小控制在50-400nm范围内。用阳离子聚合物包被后,粒径和zeta电位显著增加。MTT法表明未包被和包被的纳米颗粒对BMSC均无毒性。基于ALP诱导和钙化,聚合物包被的纳米颗粒中BMP-2的生物活性完全得以保留。
本研究描述了一种粒径可控的BSA纳米颗粒的制备方法,此类聚合物包被的BSA纳米颗粒有望成为骨再生中BMP-2局部和全身给药的递送载体。