载尼索地平的纳米结构脂质载体和固体脂质纳米粒口服给药的比较研究:制备、表征、渗透和药代动力学评价。
Comparative study of nisoldipine-loaded nanostructured lipid carriers and solid lipid nanoparticles for oral delivery: preparation, characterization, permeation and pharmacokinetic evaluation.
机构信息
a Department of Pharmaceutics , Vaagdevi Pharmacy College , Warangal , Telangana , India.
b Department of Pharmaceutics , KIPS , Warangal , Telangana , India.
出版信息
Artif Cells Nanomed Biotechnol. 2018;46(sup2):616-625. doi: 10.1080/21691401.2018.1465068. Epub 2018 Apr 24.
Nisoldipine (ND) has low oral bioavailability (5%) due to first-pass metabolism. Previously, solid lipid nanoparticles (SLNs) of ND were reported. In this study, nanostructured lipid carriers (NLCs) of ND are developed to enhance the oral bioavailability. ND-NLCs were prepared using hot homogenization-ultrasonication method, using oleic acid and trimyristate as liquid lipid and solid lipid, respectively. Prepared NLCs are evaluated for an optimal system using measuring size, zeta potential, entrapment efficiency, in-vitro release and in-situ absorption studies. Further, in vivo pharmacokinetic (PK) studies of NLC were conducted in rats comparison with SLN and suspension as controls. Size, ZP and EE of optimized NLCs were found to be 110.4 ± 2.95 nm, -29.4 ± 2.05 mV and 97.07 ± 2.27%, respectively. Drug loaded into NLCs was converted to amorphous form revealed by differential scanning calorimeter (DSC) and X-ray diffractometry (XRD) technique and nearly spherical in shape by scanning electron microscopy (SEM) studies. Drug release and absorption of ND were prolonged from ND-NLCs and ND-SLNs. From the PK results, NLCs showed 2.46 and 1.09-folds improvement in oral bioavailability of ND compared with suspension and SLNs formulations, respectively. Taken together, the NLCs and SLNs are used as carriers for the enhancement of oral bioavailability of the ND.
硝苯地平(ND)由于首过代谢而具有低口服生物利用度(5%)。先前已经报道了 ND 的固体脂质纳米粒(SLN)。在这项研究中,开发了 ND 的纳米结构脂质载体(NLC)以提高口服生物利用度。ND-NLC 是通过热匀化-超声法制备的,分别使用油酸和三硬脂酸甘油酯作为液体脂质和固体脂质。使用测量粒径、Zeta 电位、包封效率、体外释放和体内吸收研究来评估制备的 NLC 以获得最佳系统。此外,与 SLN 和混悬剂作为对照,在大鼠中进行了 NLC 的体内药代动力学(PK)研究。优化的 NLC 的粒径、Zeta 电位和 EE 分别为 110.4 ± 2.95nm、-29.4 ± 2.05mV 和 97.07 ± 2.27%。通过差示扫描量热法(DSC)和 X 射线衍射(XRD)技术发现,负载在 NLC 中的药物转化为无定形形式,通过扫描电子显微镜(SEM)研究发现其为近球形。ND 的药物释放和吸收从 ND-NLC 和 ND-SLN 中得到延长。从 PK 结果来看,与混悬剂和 SLN 制剂相比,NLC 使 ND 的口服生物利用度分别提高了 2.46 和 1.09 倍。综上所述,NLC 和 SLN 可作为增强 ND 口服生物利用度的载体。