Solid lipid nanoparticles for pulmonary delivery of insulin

• Published in: International journal of pharmaceutics 2008-05, Vol.356 (1), p.333-344
• Main Authors: Liu, Jie, Gong, Tao, Fu, Hualin, Wang, Changguang, Wang, Xiuli, Chen, Qian, Zhang, Qin, He, Qin, Zhang, Zhirong
• Format: Article
• Language: English
• Subjects: Administration, Inhalation; Aerosols; Animals; Bioavailability; Biological and medical sciences; Biological Availability; Blood Glucose - drug effects; Cell Line, Tumor; Diabetes Mellitus, Experimental - drug therapy; Drug Delivery Systems; Drug Stability; General pharmacology; Glycine max - chemistry; Humans; Hypoglycemic Agents - administration & dosage; Hypoglycemic Agents - pharmacokinetics; Hypoglycemic Agents - toxicity; Hypoglycemic effect; Insulin; Insulin - administration & dosage; Insulin - pharmacokinetics; Insulin - toxicity; Male; Medical sciences; Nanoparticles; Nebulization; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Phosphatidylcholines - chemistry; Pulmonary Alveoli - metabolism; Rats; Rats, Sprague-Dawley; Sodium Cholate - chemistry; Solid lipid nanoparticles; Tissue Distribution
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2008.01.008

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 μIU/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.