Preparation and optimization of matrix metalloproteinase-1-loaded poly(lactide-co-glycolide-co-caprolactone) nanoparticles with rotatable central composite design and response surface methodology.
Preparation and optimization of matrix metalloproteinase-1-loaded poly(lactide-co-glycolide-co-caprolactone) nanoparticles with rotatable central composite design and response surface methodology.
复制标题
采用可旋转中心复合材料设计和响应面法制备和优化负载基质金属蛋白酶1的聚(丙交酯-乙交酯-己内酯)纳米粒子
DOI：
10.1186/1556-276x-7-359
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发表时间：
2012-07-02
影响因子：
--
通讯作者：
Geng H
中科院分区：
文献类型：
--
作者：
Sun P;Song H;Cui D;Qi J;Xu M;Geng H
基质金属蛋白酶是细胞外基质分解和炎症过程中的关键调节分子。基质金属蛋白酶-1（MMP-1）通过促进肌纤维的形成和纤维组织的退变而显著促进肌肉再生。在此，我们制备了新型的MMP-1负载的聚（丙交酯-共-乙交酯-共-己内酯）（PLGA-PCL）纳米颗粒（NP）能够持续释放MMP-1。以二次方程组为数学模型，采用旋转中心组合设计和响应面法对纳米粒的制备工艺进行优化。然后，对优化的纳米粒进行表征，包括粒径分布、颗粒形态、药物包封率、MMP-1活性测定和MMP-1从纳米粒的体外释放。数学建模结果表明，制备负载MMP-1的纳米粒的最佳条件为：均质时间7 min、均质搅拌速度4.5 krpm、有机溶剂相与外水相的体积比0.4。纳米粒的包封率为38.75 ± 4.74%，平均粒径为322.7 ± 18.1nm。进一步的扫描电子显微镜图像显示纳米颗粒具有光滑和球形的表面，平均粒径约为300 nm。MMP-1活性测定和体外药物释放曲线表明，该酶的生物活性可以保留，其中封装允许MMP-1超过60天的延长释放。综上所述，我们在这里报道了用于持续释放MMP-1的新型PLGA-PCL NPs，这可能为组织重建治疗提供理想的MMP-1递送方法。
Matrix metalloproteases are key regulatory molecules in the breakdown of extracellular matrix and in inflammatory processes. Matrix metalloproteinase-1 (MMP-1) can significantly enhance muscle regeneration by promoting the formation of myofibers and degenerating the fibrous tissue. Herein, we prepared novel MMP-1-loaded poly(lactide-co-glycolide-co-caprolactone) (PLGA-PCL) nanoparticles (NPs) capable of sustained release of MMP-1. We established quadratic equations as mathematical models and employed rotatable central composite design and response surface methodology to optimize the preparation procedure of the NPs. Then, characterization of the optimized NPs with respect to particle size distribution, particle morphology, drug encapsulation efficiency, MMP-1 activity assay andin vitrorelease of MMP-1 from NPs was carried out. The results of mathematical modeling show that the optimal conditions for the preparation of MMP-1-loaded NPs were as follows: 7 min for the duration time of homogenization, 4.5 krpm for the agitation speed of homogenization and 0.4 for the volume ratio of organic solvent phase to external aqueous phase. The entrapment efficiency and the average particle size of the NPs were 38.75 ± 4.74% and 322.7 ± 18.1 nm, respectively. Further scanning electron microscopy image shows that the NPs have a smooth and spherical surface, with mean particle size around 300 nm. The MMP-1 activity assay andin vitrodrug release profile of NPs indicated that the bioactivity of the enzyme can be reserved where the encapsulation allows prolonged release of MMP-1 over 60 days. Taken together, we reported here novel PLGA-PCL NPs for sustained release of MMP-1, which may provide an ideal MMP-1 delivery approach for tissue reconstruction therapy.