Ogunwuyi O, Adesina S, Akala E O
Pharmazie. 2015 Mar;70(3):165-76.
We report here our efforts on the development of stealth biodegradable crosslinked poly-ε-caprolactone nanoparticles by free radical dispersion polymerization suitable for the delivery of bioactive agents. The uniqueness of the dispersion polymerization technique is that it is surfactant free, thereby obviating the problems known to be associated with the use of surfactants in the fabrication of nanoparticles for biomedical applications. Aided by a statistical software for experimental design and analysis, we used D-optimal mixture statistical experimental design to generate thirty batches of nanoparticles prepared by varying the proportion of the components (poly-ε-caprolactone macromonomer, crosslinker, initiators and stabilizer) in acetone/water system. Morphology of the nanoparticles was examined using scanning electron microscopy (SEM). Particle size and zeta potential were measured by dynamic light scattering (DLS). Scheffe polynomial models were generated to predict particle size (nm) and particle surface zeta potential (mV) as functions of the proportion of the components. Solutions were returned from simultaneous optimization of the response variables for component combinations to (a) minimize nanoparticle size (small nanoparticles are internalized into disease organs easily, avoid reticuloendothelial clearance and lung filtration) and (b) maximization of the negative zeta potential values, as it is known that, following injection into the blood stream, nanoparticles with a positive zeta potential pose a threat of causing transient embolism and rapid clearance compared to negatively charged particles. In vitro availability isotherms show that the nanoparticles sustained the release of docetaxel for 72 to 120 hours depending on the formulation. The data show that nanotechnology platforms for controlled delivery of bioactive agents can be developed based on the nanoparticles.
我们在此报告通过自由基分散聚合法开发隐形可生物降解交联聚己内酯纳米颗粒的工作，该纳米颗粒适用于生物活性剂的递送。分散聚合技术的独特之处在于它不含表面活性剂，从而避免了在制备用于生物医学应用的纳米颗粒时使用表面活性剂所带来的已知问题。在一个用于实验设计和分析的统计软件的辅助下，我们使用D - 最优混合统计实验设计，通过改变丙酮/水体系中各组分（聚己内酯大分子单体、交联剂、引发剂和稳定剂）的比例来制备三十批纳米颗粒。使用扫描电子显微镜（SEM）检查纳米颗粒的形态。通过动态光散射（DLS）测量粒径和zeta电位。生成Scheffe多项式模型以预测粒径（纳米）和颗粒表面zeta电位（毫伏）作为各组分比例的函数。通过对响应变量进行同时优化，从组分组合中得到的溶液可用于：（a）最小化纳米颗粒尺寸（小纳米颗粒易于内化进入患病器官，避免网状内皮系统清除和肺部过滤），以及（b）最大化负zeta电位值，因为众所周知，与带负电荷的颗粒相比，注射到血流中的带正zeta电位的纳米颗粒有导致短暂栓塞和快速清除的风险。体外释放等温线表明，根据配方不同，纳米颗粒可持续释放多西他赛72至120小时。数据表明，可以基于这些纳米颗粒开发用于生物活性剂控释的纳米技术平台。
