School of Pharmaceutical Science, Shandong University, Ji'nan 250012, PR China.
J Biomed Nanotechnol. 2009 Feb;5(1):84-92. doi: 10.1166/jbn.2009.036.
Growing attentions have been paid to the pulmonary route for systemic delivery of peptide and protein drugs, such as insulin. Advantages of this non-injective route include rapid drug deposition in the target organ, fewer systemic side effects and avoiding first pass metabolism. However, sustained release formulations for pulmonary delivery have not been fully exploited till now. In our study, a novel dry powder inhalation (DPI) system of insulin loaded solid lipid nanoparticles (Ins-SLNs) was investigated for prolonged drug release, improved stability and effective inhalation. Firstly, the drug was incorporated into the lipid carriers for a maximum entrapment efficiency as high as 69.47 +/- 3.27% (n = 3). Secondly, DPI formulation was prepared by spray freeze drying of Ins-SLNs suspension, with optimized lyoprotectant and technique parameters in this procedure. The properties of DPI particles were characterized for their pulmonary delivery potency. Thirdly, the in vivo study of intratracheal instillation of Ins-SLNs to diabetic rats showed prolonged hypoglycemic effect and a relative pharmacological bioavailability of 44.40% could be achieved in the group of 8 IU/kg dosage. These results indicated that SLNs have shown increasing potential as an efficient and non-toxic lipophilic colloidal drug carrier for enhanced pulmonary delivery of insulin.
人们越来越关注肽类和蛋白质类药物（如胰岛素）的肺部给药途径。与注射途径相比，这种非注射途径具有药物能快速沉积在靶器官、全身副作用较少和避免首过代谢等优点。然而，直到现在，肺部给药的持续释放制剂仍未得到充分开发。在我们的研究中，考察了一种新型的载胰岛素固体脂质纳米粒（Ins-SLNs）干粉吸入（DPI）系统，以实现药物的长效释放、提高稳定性和有效吸入。首先，将药物包载于脂质载体中，最大包封率高达 69.47 +/- 3.27%（n = 3）。其次，通过喷雾冷冻干燥 Ins-SLNs 混悬液制备 DPI 制剂，并对该过程中的赋形剂和技术参数进行了优化。对 DPI 颗粒的性质进行了表征，以评估其肺部给药能力。第三，通过气管内滴注 Ins-SLNs 对糖尿病大鼠的体内研究表明，该给药系统能延长降血糖作用，在 8IU/kg 剂量组中，相对药物生物利用度可达 44.40%。这些结果表明，SLNs 作为一种有效的、无毒的亲脂性胶体药物载体，在增强胰岛素的肺部递送上具有越来越大的潜力。
