title: 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.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: College of Pharmacy, Pusan National University, 30 Jangjeon-dong, Geumjeong-gu, Busan 609-735, Republic of Korea.
authors.forename: Hyunuk
authors.initials: H
authors.lastname: Kim
authors.forename: Juho
authors.initials: J
authors.lastname: Lee
authors.forename: Tae Hyung
authors.initials: TH
authors.lastname: Kim
authors.forename: Eun Seong
authors.initials: ES
authors.lastname: Lee
authors.forename: Kyung Taek
authors.initials: KT
authors.lastname: Oh
authors.forename: Don Haeng
authors.initials: DH
authors.lastname: Lee
authors.forename: Eun-Seok
authors.initials: ES
authors.lastname: Park
authors.forename: You Han
authors.initials: YH
authors.lastname: Bae
authors.forename: Kang Choon
authors.initials: KC
authors.lastname: Lee
authors.forename: Yu Seok
authors.initials: YS
authors.lastname: Youn
mesh_terms: D000280:Administration, Inhalation; D000418:Albumins / Q000737:chemistry*; D000818:Animals; D045744:Cell Line, Tumor; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D016503:Drug Delivery Systems / Q000379:methods; D045703:Emulsifying Agents / Q000737:chemistry; D005022:Ethyldimethylaminopropyl Carbodiimide / Q000737:chemistry; D000077270:Exenatide; D006801:Humans; D007004:Hypoglycemic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D019344:Lactic Acid / Q000737:chemistry*; D008168:Lung / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D008863:Microspheres; D010169:Palmitic Acids / Q000737:chemistry; D010316:Particle Size; D010455:Peptides / Q000737:chemistry* / Q000494:pharmacology*; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D016062:Porosity; D014688:Venoms / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000418:Albumins; D045703:Emulsifying Agents; D007004:Hypoglycemic Agents; D010169:Palmitic Acids; D010455:Peptides; D014688:Venoms; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D000077270:Exenatide; D005022:Ethyldimethylaminopropyl Carbodiimide