Repaglinide-loaded nanostructured lipid carriers (REP-NLCs) with different particle sizes were successfully designed and prepared to investigate the permeation and absorption ability by in situ single-pass intestinal perfusion (SPIP) study and pharmacokinetics. Both of the formulations prepared by solvent diffusion method exhibited a spherical shape under transmission electron microscopy (TEM) and similar zeta potential value of -11 mV. The particles size, encapsulation efficiency (EE), drug loading (DL) of REP-NLCs-Small and REP-NLCs-Large size preparations were about 79 nm and 325 nm, 96.83% and 98.60%, 4.41% and 3.05%, respectively. Besides, both REP-NLCs showed good colloidal stability and had no burst release phenomenon compared with REP-Sol. SPIP demonstrated the improved membrane permeability for NLCs compared with REP-Sol, especially NLCs-Small size preparation. The bioavailability increased sequentially in REP-Sol, REP-NLCs-Large, and REP-NLCs-Small, and the difference between each other was statistical significant. Our investigations demonstrate that NLCs with small particles size of 50-100 nm, such as 79 nm, are able to enhance absorption performance of a poorly soluble repaglinide compared with large particles size, such as 325 nm, by significantly improving the absorption in jejunum, and colon of rats and thus well improving oral bioavailability.

中文翻译：

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用于改善口服吸收的不同粒径的瑞格列奈负载纳米结构脂质载体：制备、表征、药代动力学和原位肠道灌注。

成功设计并制备了载有瑞格列奈的纳米结构脂质载体（REP-NLCs），通过原位单程肠道灌注（SPIP）研究和药代动力学研究其渗透和吸收能力。通过溶剂扩散法制备的两种制剂在透射电子显微镜 (TEM) 下均呈球形，zeta 电位值相似，为 -11 mV。REP-NLCs-Small 和 REP-NLCs-Large 制剂的粒径、包封率（EE）、载药量（DL）分别约为 79 nm 和 325 nm，分别为 96.83% 和 98.60%、4.41% 和 3.05% . 此外，与 REP-Sol 相比，两种 REP-NLC 均表现出良好的胶体稳定性，并且没有爆发释放现象。与 REP-Sol 相比，SPIP 证明了 NLC 的膜渗透性提高，特别是 NLCs-小尺寸制备。REP-Sol、REP-NLCs-Large和REP-NLCs-Small的生物利用度依次增加，且彼此间的差异有统计学意义。我们的研究表明，与大粒径（例如 325 nm）相比，50-100 nm（例如 79 nm）的小粒径 NLC 能够通过显着改善空肠中的吸收来增强难溶性瑞格列奈的吸收性能，和大鼠结肠，从而很好地提高口服生物利用度。