Hedberg Elizabeth L, Tang Andrew, Crowther Roger S, Carney Darrell H, Mikos Antonios G
Department of Bioengineering, Rice University, PO Box 1892, MS-142, Houston, TX 77251-1892, USA.
J Control Release. 2002 Dec 5;84(3):137-50. doi: 10.1016/s0168-3659(02)00261-4.
Poly(D,L-lactic-co-glycolic acid)/poly(ethylene glycol) (PLGA/PEG) blend microparticles loaded with the osteogenic peptide TP508 were added to a mixture of poly(propylene fumarate) (PPF), poly(propylene fumarate)-diacrylate (PPF-DA), and sodium chloride (NaCl) for the fabrication of PPF composite scaffolds that could allow for tissue ingrowth as well as for the controlled release of TP508 when implanted in an orthopedic defect site. In this study, PPF composites were fabricated and the in vitro release kinetics of TP508 were determined. TP508 loading within the PLGA/PEG microparticles, PEG content within the PLGA/PEG microparticles, the microparticle content of the PPF composite polymer component, and the leachable porogen initial mass percent of the PPF composites were varied according to a fractional factorial design and the effect of each variable on the release kinetics was determined for up to 28 days. Each composite formulation released TP508 with a unique release profile. The initial release (release through day 1) of the PLGA/PEG microparticles was reduced upon inclusion in the PPF composite formulations. Day 1 normalized cumulative mass release from PPF composites ranged from 0.14+/-0.01 to 0.41+/-0.01, whereas the release from PLGA/PEG microparticles ranged from 0.31+/-0.02 to 0.58+/-0.01. After 28 days, PPF composites released 53+/-4% to 86+/-2% of the entrapped peptide resulting in cumulative mass releases ranging from 0.14+/-0.01 microg TP508/mm(3) scaffold to 2.46+/-0.05 microg TP508/mm(3) scaffold. The results presented here demonstrate that PPF composites can be used for the controlled release of TP508 and that alterations in the composite's composition can lead to modulation of the TP508 release kinetics. These composites can be used to explore the effects varied release kinetics and dosages on the formation of bone in vivo.
将负载有成骨肽TP508的聚（D，L-乳酸-共-乙醇酸）/聚（乙二醇）（PLGA/PEG）共混微粒添加到聚富马酸丙二醇酯（PPF）、聚富马酸丙二醇酯-二丙烯酸酯（PPF-DA）和氯化钠（NaCl）的混合物中，用于制备PPF复合支架，该支架在植入骨科缺损部位时能够促进组织向内生长并实现TP508的控释。在本研究中，制备了PPF复合材料并测定了TP508的体外释放动力学。根据分数析因设计改变PLGA/PEG微粒内的TP508负载量、PLGA/PEG微粒内的PEG含量、PPF复合聚合物组分的微粒含量以及PPF复合材料的可沥滤致孔剂初始质量百分比，并确定每个变量对长达28天的释放动力学的影响。每种复合制剂释放TP508时都具有独特的释放曲线。当包含在PPF复合制剂中时，PLGA/PEG微粒的初始释放（第1天的释放）减少。PPF复合材料第1天的归一化累积质量释放范围为0.14±0.01至0.41±0.01，而PLGA/PEG微粒的释放范围为0.31±0.02至0.58±0.01。28天后，PPF复合材料释放了53±4%至86±2%的包封肽，导致累积质量释放范围为0.14±0.01μg TP508/mm³支架至2.46±0.05μg TP508/mm³支架。此处呈现的结果表明，PPF复合材料可用于TP508的控释，并且复合材料组成的改变可导致TP508释放动力学的调节。这些复合材料可用于探索不同的释放动力学和剂量对体内骨形成的影响。
