Comparative study of nisoldipine-loaded nanostructured lipid carriers and solid lipid nanoparticles for oral delivery: preparation, characterization, permeation and pharmacokinetic evaluation
Comparative study of nisoldipine-loaded nanostructured lipid carriers and solid lipid nanoparticles for oral delivery: preparation, characterization, permeation and pharmacokinetic evaluation
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DOI：
10.1080/21691401.2018.1465068
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发表时间：
2018-01-01
影响因子：
5.8
通讯作者：
Gorre, Thirupathi
中科院分区：
文献类型：
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作者：
Dudhipala, Narendar;Janga, Karthik Yadav;Gorre, Thirupathi
尼索地平(ND)口服生物利用度低(5%)，为首过代谢。此前，ND的固体脂质纳米粒(SLN)已有报道。在本研究中，开发了ND的纳米结构脂质载体(NLCS)以提高口服生物利用度。分别以油酸和三聚氰酸酯为液体脂和固体脂，采用热均质-超声法制备了ND-NLCs。通过测量大小、Zeta电位、包封率、体外释放和原位吸收研究，评价所制备的NLC的最佳系统。进一步，以SLN和混悬液为对照，进行了NLC在大鼠体内的药代动力学研究。优化后的NLCS尺寸、ZP和EE分别为110.4+/-2.95 nm、-29.4+/-2.05 mV和97.07+/-2.27%。差示扫描量热仪(DSC)和X射线衍射仪(X射线衍射仪)表明，负载到NLCS中的药物转变为无定形，扫描电子显微镜(SEM)研究表明药物呈近球形。ND-NLCS和ND-SLNS的药物释放和吸收均延长。从PK结果来看，NLCS显示ND的口服生物利用度分别是混悬剂和SLNS制剂的2.46倍和1.09倍。综上所述，NLCS和SLN可作为提高ND口服生物利用度的载体。
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.