This study was aimed at developing a polymeric drug delivery system for a steroidal aromatase inhibitor, exemestane (exe) intended for sustained targeted delivery of drug through intravenous route. Carboxylated polycaprolactone (cPCL) was synthesized by ring opening polymerization of caprolactone. Exe-loaded cPCL nanoparticles (NPs) were prepared by interfacial deposition of preformed polymer and characterized. A 3-factor, 3-level Box–Behnken design was used to derive a second-order polynomial equation and construct contour and response plots for maximized response of percentage drug entrapment (PDE) with constraints on particle size (PS). The independent variables selected were ratio of exe/cPCL, amount of cPCL, and volume of organic phase. Polymerization of caprolactone to cPCL was confirmed by Fourier transform infrared (FTIR) and gel permeation chromatography. The prepared NPs were evaluated for differential scanning calorimetry (DSC), transmission electron microscopy (TEM), and in vitro release studies. Optimum formulation based on desirability (1.0) exhibited PDE of 83.96 % and PS of 180.5 nm. Check point analysis confirmed the role of the derived polynomial equation and contour plots in predicting the responses. Zeta potential of optimized formulation was −33.8 ± 2.1 mV. DSC studies confirmed the absence of any interaction between drug and polymer. TEM image showed non-aggregated and spherical shaped NPs. Drug release from NPs showed sustained release and followed Korsmeyer–Peppas model, indicating Fickian drug release. Thus, preparation of exe-loaded cPCL NPs with high PDE and desired PS suitable for providing passive targeting could be statistically optimized using Box–Behnken design.

中文翻译：

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依西美坦在聚己内酯纳米颗粒中的包封：优化，表征和释放动力学。

这项研究的目的是开发一种用于甾体芳香酶抑制剂Exemestane（exe）的聚合物药物递送系统，旨在通过静脉内途径持续靶向药物递送。通过己内酯的开环聚合来合成羧基化的聚己内酯（cPCL）。通过预先形成的聚合物的界面沉积法制备了Exe加载的cPCL纳米颗粒（NPs）并进行了表征。使用三因素，三级Box-Behnken设计来导出二阶多项式方程，并构建轮廓和响应图，以最大程度地限制颗粒度（PS）的药物截留百分比（PDE）的响应。选择的独立变量是exe / cPCL的比例，cPCL的量和有机相的体积。通过傅里叶变换红外光谱（FTIR）和凝胶渗透色谱法证实己内酯聚合成cPCL。对制备的NP进行差示扫描量热法（DSC），透射电子显微镜（TEM）和体外释放研究进行评估。基于期望值（1.0）的最佳配方显示PDE为83.96％，PS为180.5 nm。检查点分析证实了导出的多项式方程式和轮廓图在预测响应中的作用。优化配方的ζ电势为-33.8±2.1 mV。DSC研究证实药物和聚合物之间不存在任何相互作用。TEM图像显示非聚集的球形NP。NPs的药物释放显示出持续释放，并遵循Korsmeyer-Peppas模型，表明Fickian药物释放。因此，