Strontium ranelate-loaded PLGA porous microspheres enhancing the osteogenesis of MC3T3-E1 cells

Strontium ranelate-loaded PLGA porous microspheres enhancing the osteogenesis of MC3T3-E1 cells
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负载雷奈酸锶的PLGA多孔微球增强MC3T3-E1细胞的成骨作用

DOI:
10.1039/c7ra01445g
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发表时间:
2017-01-01
期刊:
影响因子:
3.9
通讯作者:
Dai, Kerong
Dai, Kerong
中科院分区:
化学3区
文献类型:
--
作者:
Mao, Zhenyang;Fang, Zhiwei;Dai, Kerong

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可生物降解的聚乳酸-羟基乙酸共聚物(PLGA)已被用作组织工程支架以及用于递送蛋白质、药物和其他大分子的载体。羟基磷灰石(HA)纳米粒子在PLGA微球表面的自组装可以创造一个亲水环境,其氢氧化物可以中和PLGA降解产物的酸性。这些微球可用于递送雷奈酸锶(SR),其用于治疗骨质疏松症。在本研究中,我们制备了多孔PLGA微球(PM),SR负载(SR-)PM,和SR-PM与HA纳米悬浮液和聚乙烯醇(PVA)作为表面活性剂(SR-PM-HA)在S/O/Ns方法。该微球具有相互连通的多孔结构。与SR-PM-HA的85%相比,SR-PM-HA的SR累积释放百分比在22天内为90%。在这两种情况下,药物释放是逐渐的(没有爆发释放)。SR-PM和SR-PM-HA类似地刺激MC 3 T3-E1细胞的增殖至比PM更大的程度并且诱导成骨分化,如通过碱性磷酸酶染色和成骨标记基因表达的实时PCR分析所确定的。这些结果表明,SR-PM-HA是生物相容性和适合于药物输送和骨诱导。
Biodegradable poly lactic-co-glycolic acid (PLGA) has been used as a tissue engineering scaffold as well as a carrier for the delivery of proteins, drugs, and other macromolecules. Hydroxyapatite (HA) nanoparticle self-assembly on the surface of a PLGA microsphere can create a hydrophilic environment, and its hydroxide can neutralize the acidity of PLGA degradation products. These microspheres can be used to deliver strontium ranelate (SR), which is used to treat osteoporosis. In the present study, we fabricated porous PLGA microspheres (PM), SR-loaded (SR-)PM, and SR-PM with HA nanosuspension and polyvinyl alcohol (PVA) as a surfactant (SR-PM-HA) in a S/O/Ns method. The microspheres exhibited an interconnected porous structure. The percent cumulative release of SR from SR-PM was 90% in 22 days as compared to 85% from SR-PM-HA. In both cases, drug release was gradual (with no burst release). SR-PM and SR-PM-HA similarly stimulated the proliferation of MC3T3-E1 cells to a greater degree than PM and induced osteogenic differentiation, as determined by alkaline phosphatase staining and real-time PCR analysis of osteogenic marker gene expression. These results indicate that SR-PM-HA is biocompatible and suitable for drug delivery and osteoinduction.