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果胶微球-磷酸钙复合骨水泥的控制释放性能和最终大孔率。

Controlled release properties and final macroporosity of a pectin microspheres-calcium phosphate composite bone cement.

机构信息

Université de Toulouse, CIRIMAT, UPS-INPT-CNRS, Faculté de Pharmacie, 118 Route de Narbonne, 31062 Toulouse Cedex 4, France.

出版信息

Acta Biomater. 2010 Jun;6(6):2294-300. doi: 10.1016/j.actbio.2009.11.019. Epub 2009 Dec 4.

Abstract

The use of calcium phosphate cements (CPC) is restricted by their lack of macroporosity and poor drug release properties. To overcome these two limitations, incorporating degradable polymer microparticles into CPC is an attractive option, as polymer microparticles could help to control drug release and induce macroporosity after degradation. Although few authors have yet tested synthetic polymers, the potentiality of polysaccharides' assuming this role has never been explored. Low-methoxy amidated pectins (LMAP) constitute valuable candidates because of their biocompatibility and ionic and pH sensitivity. In this study, the potentiality of a LMAP with a degree of esterification (DE) of 30 and a degree of amidation (DA) of 19 was explored. The aim of this study was to explore the influence of LMAP microspheres within the composite on the cement properties, drug release ability and final macroporosity after microspheres degradation. Three LMAP incorporation ratios, 2%, 4% and 6% w/w were tested, and ibuprofen was chosen as the model drug. In comparison with the CPC reference, the resulting composites presented reduced setting times and lowered the mechanical properties, which remained acceptable for an implantation in moderate-stress-bearing locations. Sustained release of ibuprofen was obtained on at least 45days, and release rates were found to be controlled by the LMAP ratio, which modulated drug diffusion. After 4months of degradation study, the resulting CPC appeared macroporous, with a maximum macroporosity of nearly 30% for the highest LMAP incorporation ratio, and interconnectivity between pores could be observed. In conclusion, LMAP appear as interesting candidates to generate macroporous bone cements with tailored release properties and macroporosity by adjusting the pectin content within the composites.

摘要

磷酸钙骨水泥(CPC)的应用受到其缺乏大孔结构和药物释放性能差的限制。为了克服这两个限制,将可降解聚合物微球掺入 CPC 中是一种很有吸引力的选择,因为聚合物微球可以帮助控制药物释放,并在降解后诱导大孔结构。尽管很少有作者测试过合成聚合物,但从未探索过多糖在这方面的潜力。低甲氧基酰胺化果胶(LMAP)由于其生物相容性、离子和 pH 敏感性而成为有价值的候选材料。在这项研究中,研究了酯化度(DE)为 30 和酰胺化度(DA)为 19 的 LMAP 的潜力。本研究的目的是探索在复合材料中 LMAP 微球对水泥性能、药物释放能力以及微球降解后最终大孔率的影响。测试了 3 种 LMAP 掺入比,即 2%、4%和 6%(w/w),并选择布洛芬作为模型药物。与 CPC 参考物相比,所得复合材料的凝固时间缩短,力学性能降低,但仍可接受植入中度承重部位。至少 45 天可获得布洛芬的持续释放,发现释放速率受 LMAP 比例的控制,从而调节药物扩散。在 4 个月的降解研究后,所得 CPC 呈现出大孔结构,最高 LMAP 掺入比的最大大孔率接近 30%,并且可以观察到孔之间的连通性。总之,LMAP 作为具有可调节释放性能和大孔率的大孔骨水泥的候选材料,通过调整复合材料中的果胶含量,具有很大的潜力。

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