基于黏液的纳米粒的配方与评价用于依泽替米贝的有效传递

INTRODUCTION: The aim of current study was to prepare mucilage (LUM) based nanoparticles, capable of encapsulating hydrophobic drug ezetimibe as nanocarriers. METHODS: Solvent evaporation and nanoprecipitation techniques were used to develop nanoparticles by encapsulating ezetimibe in the articulated matrix of polysaccharide fractions. Developed nanoparticles were characterized to determine the particle size, zeta potential, polydispersibility index (PDI), and entrapment efficiency (EE). Morphology and physicochemical characterization were carried out through SEM, FTIR, PXRD and thermal analysis. Saturation solubility and in vitro release studies were also performed. Safety assessment of ezetimibe loaded nanoparticles was evaluated via oral acute toxicity study. RESULTS: The mean particle size, zeta potential, PDI and EE for emulsion solvent evaporation were 683.6 nm, -28.3 mV, 0.39, 63.7% and for nanoprecipitation were 637.7 nm, 0.07, -27.1 mV and 80%, respectively. Thermal analysis confirmed enhanced thermal stability, whereas PXRD confirmed amorphous nature of drug. Saturation solubility (p-value <0.05) demonstrated improved solubility of drug when enclosed in linseed nanoparticles. Nanoprecipitation surpasses emulsion solvent evaporation in dissolution test by possessing smaller size. Acute oral toxicity study indicated no signiﬁcant changes in behavioral, clinical or histopathological parameters of control and experimental groups. CONCLUSION: The in vitro release of ezetimibe was augmented by enhancing aqueous solubility through devised nanoparticles. Thus, linseed mucilage could act as biopolymer in the fabrication of nanoparticle formulation. The acute oral toxicological investigations provided evidence that LUMNs were safe after oral administration.

简介：本研究旨在制备以黏液素（LUM）为基础的纳米粒子，将难溶于水的药物依泽替米贝作为纳米载体进行包封。

方法：采用溶剂蒸发法和纳米沉淀法，通过将依泽替米贝包埋在多糖分数的连接基质中制备纳米粒子。对所开发的纳米粒子进行特性鉴定，以确定粒径、Zeta 电位、多分散指数（PDI）和包封效率（EE）。采用扫描电子显微镜（SEM）、傅里叶变换红外光谱（FTIR）、粉末 X 射线衍射（PXRD）和热分析对形态和物理化学特性进行研究。还进行了饱和溶解度和体外释放研究。通过口服急性毒性研究评估载有依泽替米贝的纳米粒子的安全性。

结果：乳化溶剂蒸发法的平均粒径、Zeta 电位、PDI 和 EE 分别为 683.6nm、-28.3mV、0.39 和 63.7%，而纳米沉淀法分别为 637.7nm、0.07、-27.1mV 和 80%。热分析证实药物的热稳定性增强，而 X 射线衍射分析（PXRD）证实药物呈非晶态。药物包封在亚麻籽油纳米粒子中后，其溶解度显著提高（p 值<0.05）。在溶解试验中，纳米沉淀法优于乳化溶剂蒸发法，因为纳米沉淀法具有更小的粒径。急性口服毒性研究表明，对照组和实验组的行为、临床或组织病理学参数均无显著变化。

结论：通过设计的纳米粒子提高了依泽替米贝的水溶解度，从而增强了其体外释放。因此，亚麻籽油黏液素可作为生物聚合物用于纳米粒制剂的制备。急性口服毒性研究提供了证据，表明 LUMN 经口服给药后是安全的。