Solid lipid nanoparticles for pulmonary delivery of insulin
Solid lipid nanoparticles for pulmonary delivery of insulin
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DOI：
10.1016/j.ijpharm.2008.01.008
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发表时间：
2008-05-22
影响因子：
5.8
通讯作者：
Zhang, Zhirong
中科院分区：
文献类型：
--
作者：
Liu, He;Gong, Tao;Zhang, Zhirong
越来越多的人注意到肺途径作为治疗药物非侵入性全身递送的替代方案的潜力。本研究采用反胶束双乳法，制备了一种新型雾化器兼容固体脂质纳米颗粒（SLNs），用于胰岛素肺给药。研究了胆酸钠（SC）和大豆磷脂酰胆碱（SPC）用量对纳米颗粒沉积性能的影响。在最优条件下，SLNs的包封量（ED）、可吸入分数（RF）和雾化效率（NE）分别达到96.53%、82.11%和63.28%，且在雾化过程中保持稳定。肺给药20 IU/kg Ins-SLNs 4 h后，空腹血糖水平降至39.41%，胰岛素水平升高至约170 mu IU/ml。以皮下注射为对照，其药理生物利用度为24.33%，相对生物利用度为22.33%。将荧光标记的胰岛素加入到sln中，我们发现sln有效且均匀地分布在肺泡中。这些发现表明，sln可以作为胰岛素肺递送的潜在载体，提高体外和体内稳定性，延长降糖作用，从而不可避免地提高生物利用度。(c) 2008 Elsevier B.V.版权所有
Growing attention has been given to the potential of pulmonary route as an alternative for non-invasive systemic delivery of therapeutic agents. In this study, novel nebulizer-compatible solid lipid nanoparticles (SLNs) for pulmonary drug delivery of insulin were developed by reverse micelle-double emulsion method. The influences of the amount of sodium cholate (SC) and soybean phosphatidylcholine (SPC) on the deposition properties of the nanoparticles were investigated. Under optimal conditions, the entrapment delivery (ED), respirable fraction (RF) and nebulization efficiency (NE) of SLNs could reach 96.53, 82.11 and 63.28%, respectively, and Ins-SLNs remained stable during nebulization. Fasting plasma glucose level was reduced to 39.41% and insulin level was increased to approximately 170 mu IU/ml 4 h after pulmonary administration of 20 IU/kg Ins-SLNs. A pharmacological bioavailability of 24.33% and a relative bioavailability of 22.33% were obtained using subcutaneous injection as a reference. Incorporating fluorescent-labelled insulin into SLNs, we found that the SLNs were effectively and homogeneously distributed in the lung alveoli. These findings suggested that SLNs could be used as a potential carrier for pulmonary delivery of insulin by improving both in vitro and in vivo stability as well as prolonging hypoglycemic effect, which inevitably resulted in enhanced bioavailability. (c) 2008 Elsevier B.V. All rights reserved.