Biodegradable solid lipid nanoparticle flocculates for pulmonary delivery of insulin.
The aim of our study was to prepare and characterize biodegradable insulin-loaded solid lipid nanoparticles (Ins-SLNs) flocculates for the pulmonary delivery of Ins. The cationic Ins-SLNs and anionic Ins-SLNs were prepared by W/O/W emulsion technique, respectively. Then anionic Ins-SLNs were self-assembled into flocculates via electrostatic interactions with the oppositely surface charged cationic Ins-SLNs followed by lyophilized into dry powders. The maximal entrapment efficiency of cationic Ins-SLNs and anionic Ins-SLNs were 56.32 +/- 1.01% and 66.02 +/- 1.58%, respectively. Freeze-drying the Ins-SLNs flocculates yielded dry powders with desirable aerodynamic diameter of 2.04 +/- 0.17 microm and low bulk density of 0.06146 +/- 0.0045 g/cm3, suitable for inhalation. In addition, the flocculates showed high aerosolization efficiency (emitted fraction of 92.54 +/- 0.77% and respirable fraction of 66.89 +/- 3.02%). The in vivo study showed that Ins-SLNs flocculates could prolong hypoglycemic effect and a relative pharmacological bioavailability of 35.62 +/- 1.34% could be achieved after intratracheal instillation to diabetic rats at the dose of 8 IU/kg dosage. Therefore, the biodegradable SLN flocculates fabricated via charge interaction may provide a useful strategy to fabricate dry powder for pulmonary administration of protein therapeutics or antigens.
Department of Pharmaceutics, College of Pharmacy, Shandong University, Jinan 250012, China.
Xiaoyan
X
Yang
Yongjun
Y
Liu
Chunxi
C
Liu
Na
N
Zhang
D000280:Administration, Inhalation; D000818:Animals; D001786:Blood Glucose / Q000032:analysis*; D003692:Delayed-Action Preparations / Q000008:administration & dosage* / Q000737:chemistry; D003921:Diabetes Mellitus, Experimental / Q000097:blood* / Q000188:drug therapy*; D005427:Flocculation; D007004:Hypoglycemic Agents / Q000008:administration & dosage; D007328:Insulin / Q000008:administration & dosage*; D008055:Lipids / Q000737:chemistry*; D053769:Nanocapsules / Q000008:administration & dosage* / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D013311:Streptozocin; D016896:Treatment Outcome
D001786:Blood Glucose; D003692:Delayed-Action Preparations; D007004:Hypoglycemic Agents; D007328:Insulin; D008055:Lipids; D053769:Nanocapsules; D013311:Streptozocin