Preparation, characterization, and in vitro/vivo studies of oleanolic acid-loaded lactoferrin nanoparticles.
Preparation, characterization, and in vitro/vivo studies of oleanolic acid-loaded lactoferrin nanoparticles.
复制标题
DOI：
10.2147/dddt.s133997
复制
发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Zhao Z
中科院分区：
文献类型：
--
作者：
Xia X;Liu H;Lv H;Zhang J;Zhou J;Zhao Z
齐墩果酸是一种五环三萜类化合物，用于安全、经济地治疗肝病。然而，作为生物药剂学分类系统IV类药物，OA的生物利用度较低，原因是其溶解度低(<；1μg/mL)和生物膜通透性低。我们开发了一种新型的负载乳铁蛋白(LF)的乳铁蛋白纳米粒(OA-NP)纳米给药系统，该系统具有增强的体外溶出度和改善的口服吸收和生物利用度。采用NP白蛋白键合技术制备了OA-NPs，并用动态光散射、扫描电子显微镜、X射线粉末衍射、差示扫描量热法和体外溶出实验对其进行了表征。采用高效液相色谱-串联质谱法研究大鼠体内药代动力学。OA-NPs(OA：Lf=1：6，w/w%)为球形，粒径为202.2±8.3 nm，ζ电位为+(27.1±0.32)mV，包封率为92.5 9%±3.2 4%，体外释放良好。与大鼠口服后的游离药物相比，有效的体内生物利用度(340.59%)。LF新型纳米载体提高了OA的溶出度、肠道吸收和生物利用度。这些结果表明，LF NPs是一种改善难溶和吸收不良药物的口服吸收和生物利用度的新策略。
Oleanolic acid (OA), a pentacyclic triterpene, is used to safely and economically treat hepatopathy. However, OA, a Biopharmaceutics Classification System IV category drug, has low bioavailability owing to low solubility (<1 μg/mL) and biomembrane permeability. We developed a novel OA nanoparticle (OA-NP)-loaded lactoferrin (Lf) nanodelivery system with enhanced in vitro OA dissolution and improved oral absorption and bioavailability. The OA-NPs were prepared using NP albumin-bound technology and characterized using dynamic light scattering, scanning electron microscopy, X-ray powder diffraction, differential scanning calorimetry, and in vitro dissolution test. The in vivo pharmacokinetics was investigated in Sprague Dawley rats using liquid chromatography-tandem mass spectrometry. OA-NPs (OA:Lf =1:6, w/w%) exhibited spherical morphology, 202.2±8.3 nm particle size, +(27.1±0.32) mV ζ potential, 92.59%±3.24% encapsulation efficiency, and desirable in vitro release profiles. An effective in vivo bioavailability (340.59%) was achieved compared to the free drug following oral administration to rats. The Lf novel nanodelivery vehicle enhanced the dissolution rate, intestinal absorption, and bioavailability of OA. These results demonstrate that Lf NPs are a new strategy for improving oral absorption and bioavailability of poorly soluble and poorly absorbed drugs.