Purpose

Zoledronic acid (ZA) is one of the drugs used clinically for the treatment of osteoporosis, and its therapeutic effect is due to the inhibition of osteoclastic cells leading to bone resorption. The aim of this study is developing an optimization method for poly(lactide-co-glycolide) (PLGA) nanoparticles of ZA which is intended for local application to enable guided bone regeneration.

Methods

Three formulation parameters (ZA content, PLGA/Pluronic F68 ratio, and organic to aqueous phase ratio) were optimized to evaluate their effects on particle size (Y₁), polydispersity index (PDI) (Y₂), zeta potential (Y₃), and entrapment efficiency (Y₄) utilizing central composite experimental design (CCD). Interaction among components was studied by Fourier transform infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC), and X-ray diffraction analysis. Morphology of nanoparticles was visualized with transmission electron microscopy (TEM). Stability studies of nanoparticles were also carried out for 6 months.

Results

The results revealed that formulation parameters significantly affected Y₁, Y₂, Y₃, and Y₄ of the nanoparticles. The developed quadratic model showed high correlation (R² > 0.84) between predicted response and evaluated parameters. Spherical nanoparticles with low mean particle size (< 106.0 nm) and high encapsulation efficiency (> 39.54%) were obtained with the optimized nanoparticle formulation and maintained colloidal stability for 6 months.

Conclusions

The use of CCD for the optimization of ZA-loaded PLGA nanoparticles has provided accessibility to the formulation with optimum properties with less experimental procedure and therefore presents an important model for predicting the properties of nanoparticles prepared with PLGA polymer commonly used in the field of drug delivery.

中文翻译：

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优化唑来膦酸负载PLGA纳米粒子的中央复合设计

目的

唑来膦酸（ZA）是临床上用于治疗骨质疏松症的药物之一，其治疗效果是由于抑制破骨细胞导致骨吸收。这项研究的目的是为ZA的丙交酯-共-乙交酯（PLGA）纳米粒子开发一种优化方法，该方法旨在局部应用以实现引导性骨再生。

方法

优化了三个配方参数（ZA含量，PLGA / Pluronic F68比率以及有机相与水相的比率），以评估它们对粒径（Y ₁），多分散指数（PDI）（Y ₂），ζ电位（Y ₃）的影响。 ，以及利用中央复合实验设计（CCD）的包封率（Y ₄）。通过傅立叶变换红外（FTIR）光谱，差示扫描量热法（DSC）和X射线衍射分析研究了组分之间的相互作用。纳米颗粒的形态用透射电子显微镜（TEM）观察。纳米颗粒的稳定性研究也进行了6个月。

结果

结果表明，配方参数显着影响纳米颗粒的Y ₁，Y ₂，Y ₃和Y ₄。所开发的二次模型显示出 预测响应与评估参数之间的高度相关性（R ² > 0.84）。通过优化的纳米颗粒配方，获得了平均粒径低（<106.0 nm），包封效率高（> 39.54％）的球形纳米颗粒，并保持了6个月的胶体稳定性。

结论

CCD用于优化ZA负载的PLGA纳米颗粒的使用为通过较少的实验步骤获得具有最佳性能的制剂提供了便利，因此提供了一种重要的模型，用于预测用药物递送领域常用的PLGA聚合物制备的纳米颗粒的性能。