Wei Lili, Yang Yunfang, Shi Kun, Wu Jun, Zhao Wei, Mo Jingxin
Department of Pharmacy, Affiliated Hospital of Guilin Medical University Guilin, China.
Department of Cardiology, The Second Affiliated Hospital of Guilin Medical University Guilin, China.
Front Pharmacol. 2016 Sep 21;7:332. doi: 10.3389/fphar.2016.00332. eCollection 2016.
The aim of the project was to assemble two optimum solid lipid nanoparticle (SLN) formulations for oral delivery of loperamide (LPM) to treat different types of diarrhea, and to evaluate their release profiles and pharmacokinetic properties . In this work, glyceryl trimyristate (Dynasan 114) nanoparticles containing the drug LPM and sodium cholate as a stabilizer were prepared using a modified solvent evaporation technique. Two LPM-loaded SLNs, namely LPM-SLN-1 (LPM-SLN with a high ratio rate of lipid to drug) and LPM-SLN-2 (LPM-SLN with a low ratio rate of lipid to drug), were prepared by the solvent evaporation method. A change in the lipid concentration affects the characteristics of LPM-SLNs. The average sizes of the LPM-SLNs were 303 ± 18 nm and 519 ± 36 nm, separately, as analyzed by dynamic light scattering. The LPM-SLNs were found to be round with a smooth surface, as observed using a transmission electron microscope and a scanning electron microscope. The average encapsulation efficiencies were 87 ± 3.78% w/w and 84 ± 5.17%, accordingly. In the release experiments, LPM-SLNs showed a continuous release profile of LPM without any burst release. The oral bioavailability of LPM-SLNs was analyzed using Wistar rats. The relative bioavailabilities of LPM-SLNs were 227 and 153%, respectively, as compared that of the LPM tablet. There was no difference in the T between LPM-SLN-2 and the LPM tablet. In conclusion, LPM-SLN-1 significantly improved the oral bioavailability of LPM, while LPM-SLN-2 having the same swift action as the LPM tablet. These results demonstrate the potential of LPM-SLNs in the oral delivery of LPM to treat different types of diarrhea.
该项目的目的是制备两种用于口服洛哌丁胺（LPM）以治疗不同类型腹泻的最佳固体脂质纳米粒（SLN）制剂，并评估其释放曲线和药代动力学性质。在这项工作中，使用改良的溶剂蒸发技术制备了含有药物LPM和胆酸钠作为稳定剂的三肉豆蔻酸甘油酯（Dynasan 114）纳米粒。通过溶剂蒸发法制备了两种载有LPM的SLN，即LPM-SLN-1（脂质与药物比例高的LPM-SLN）和LPM-SLN-2（脂质与药物比例低的LPM-SLN）。脂质浓度的变化会影响LPM-SLN的特性。通过动态光散射分析，LPM-SLN的平均粒径分别为303±18nm和519±36nm。使用透射电子显微镜和扫描电子显微镜观察发现，LPM-SLN呈圆形且表面光滑。相应地，平均包封率分别为87±3.78%w/w和84±5.17%。在释放实验中，LPM-SLN显示出LPM的持续释放曲线，没有任何突释现象。使用Wistar大鼠分析了LPM-SLN的口服生物利用度。与LPM片剂相比，LPM-SLN的相对生物利用度分别为227%和153%。LPM-SLN-2与LPM片剂之间的T没有差异。总之，LPM-SLN-1显著提高了LPM的口服生物利用度，而LPM-SLN-2具有与LPM片剂相同的快速作用。这些结果证明了LPM-SLN在口服LPM治疗不同类型腹泻方面的潜力。
