Ruhé P Q, Boerman O C, Russel F G M, Spauwen P H M, Mikos A G, Jansen J A
Department of Biomaterials, Radboud University Nijmegen Medical Center, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands.
J Control Release. 2005 Aug 18;106(1-2):162-71. doi: 10.1016/j.jconrel.2005.04.018.
The release kinetics of recombinant human bone morphogenetic protein-2 (rhBMP-2) loaded poly(dl-lactic-co-glycolic acid)/calcium phosphate cement (PLGA/Ca-P cement) composites were studied in vivo. RhBMP-2 was radiolabeled with (131)I and entrapped within PLGA microparticles or adsorbed onto the microparticle surface. PLGA microparticles were prepared of high molecular weight (HMW) PLGA (weight average molecular weight [M(w)] 49,100+/-1700) or low molecular weight (LMW) PLGA (M(w) 5,900+/-300) and used for preparation of 30:70 wt.% PLGA/Ca-P cement composite discs. Release of 131I-rhBMP-2 loaded composites was assessed by scintigraphic imaging according to a 2(2) two-level full factorial design in the rat ectopic model during four weeks. In vivo release kinetics varied among formulations. All formulations showed slow release without initial burst, and displayed a linear release from 3 to 28 days. Release of LMW entrapped rhBMP-2 composites (1.7+/-0.3%/day) was significantly faster than release from other formulations (p<0.01). After 28 days, retention within the composites was 65+/-5%, 75+/-4%, 50+/-4% and 70+/-6% of the initial rhBMP-2 for HMW entrapped, HMW adsorbed, LMW entrapped and LMW adsorbed rhBMP-2 composites, respectively. Release from the composite was probably slowed down by an interaction of rhBMP-2 and Ca-P cement after rhBMP-2 release from PLGA microparticles. We conclude that PLGA/Ca-P cement composites can be considered as sustained slow release vehicles and that the release and retention of rhBMP-2 can be modified according to the desired profile to a limited extent.
在体内研究了负载重组人骨形态发生蛋白-2（rhBMP-2）的聚（dl-乳酸-共-乙醇酸）/磷酸钙骨水泥（PLGA/Ca-P骨水泥）复合材料的释放动力学。rhBMP-2用（131）I进行放射性标记，并包裹于PLGA微粒内或吸附在微粒表面。PLGA微粒由高分子量（HMW）PLGA（重均分子量[M(w)]49,100±1700）或低分子量（LMW）PLGA（M(w)5,900±300）制备，用于制备30:70重量百分比的PLGA/Ca-P骨水泥复合圆盘。根据2(2)两水平全因子设计，在大鼠异位模型中，通过闪烁成像评估负载131I-rhBMP-2复合材料在四周内的释放情况。体内释放动力学因配方而异。所有配方均显示出缓慢释放且无初始突释，并在3至28天内呈线性释放。低分子量包裹rhBMP-2复合材料的释放（1.7±0.3%/天）明显快于其他配方（p<0.01）。28天后，对于高分子量包裹、高分子量吸附、低分子量包裹和低分子量吸附rhBMP-2复合材料，复合材料内的保留量分别为初始rhBMP-2的65±5%、75±4%、50±4%和70±6%。rhBMP-2从PLGA微粒释放后，其与Ca-P骨水泥的相互作用可能减缓了复合材料的释放。我们得出结论，PLGA/Ca-P骨水泥复合材料可被视为持续缓慢释放载体，并且rhBMP-2的释放和保留可在一定程度上根据所需情况进行调整。
