251. Albumin-coated porous hollow poly(lactic-co-glycolic acid) microparticles bound with palmityl-acylated exendin-4 as a long-acting inhalation delivery system for the treatment of diabetes.
- Author
-
Kim H, Lee J, Kim TH, Lee ES, Oh KT, Lee DH, Park ES, Bae YH, Lee KC, and Youn YS
- Subjects
- Administration, Inhalation, Animals, Cell Line, Tumor, Drug Delivery Systems methods, Emulsifying Agents chemistry, Ethyldimethylaminopropyl Carbodiimide chemistry, Exenatide, Humans, Hypoglycemic Agents chemical synthesis, Hypoglycemic Agents chemistry, Hypoglycemic Agents pharmacology, Lung drug effects, Male, Mice, Mice, Inbred C57BL, Mice, Inbred ICR, Palmitic Acids chemistry, Particle Size, Polylactic Acid-Polyglycolic Acid Copolymer, Porosity, Albumins chemistry, Diabetes Mellitus, Type 2 drug therapy, Lactic Acid chemistry, Microspheres, Peptides chemistry, Peptides pharmacology, Polyglycolic Acid chemistry, Venoms chemistry, Venoms pharmacology
- Abstract
Purpose: To study the development of porous poly(lactic-co-glycolic acid) microparticles (PLGA MPs) coated initially with albumin and then with palmityl-acylated exendin-4 (Pal-Ex4) as an inhalation system for treating diabetes., Methods: Porous PLGA MPs were prepared by w/o/w double emulsification using hydroxypropyl-β-cyclodextrin and poly(ethylene-alt-maleic anhydride). Albumin was covalently attached to the MPs using EDC (1-(3-dimethylaminopropyl)-3-ethylcarbodiimide); Pal-Ex4 was then bound on the albumin surface. Albumin-binding degree and aerosolization efficiency were investigated. Deposition of the MPs after insufflations into the lungs of ICR mice was observed by image monitoring, and pulmonary hypoglycemic efficacies were examined in db/db mice. Cytotoxicity and histopathology induced by MPs were examined in Calu-3 and A549 cells and in the lungs of db/db mice, respectively., Results: Albumin-coating and Pal-Ex4-binding to porous MP were performed with acceptable efficiencies. Pal-Ex4-bound albumin-coated MPs (Pal-Ex4/HSA-PLGA MP) were of high porosity and had appropriate aerodynamic sizes. Furthermore, this MP was efficiently deposited throughout mouse lungs, and exhibited a prolonged hypoglycemia and no significant lung tissue damage in db/db mice., Conclusion: Pal-Ex4/HSA-PLGA MP demonstrated many meaningful pharmaceutical advantages for the treatment of diabetes, in terms of aerosolization efficiency, drug loading, sustained drug-release, and hypoglycemic duration in vivo.
- Published
- 2011
- Full Text
- View/download PDF