title: Controlled release of liraglutide using thermogelling polymers in treatment of diabetes.
abstract: In treatment of diabetes, it is much desired in clinics and challenging in pharmaceutics and material science to set up a long-acting drug delivery system. This study was aimed at constructing a new delivery system using thermogelling PEG/polyester copolymers. Liraglutide, a fatty acid-modified antidiabetic polypeptide, was selected as the model drug. The thermogelling polymers were presented by poly(ε-caprolactone-co-glycolic acid)-poly(ethylene glycol)-poly(ε-caprolactone-co-glycolic acid) (PCGA-PEG-PCGA) and poly(lactic acid-co-glycolic acid)-poly(ethylene glycol)-poly(lactic acid-co-glycolic acid) (PLGA-PEG-PLGA). Both the copolymers were soluble in water, and their concentrated solutions underwent temperature-induced sol-gel transitions. The drug-loaded polymer solutions were injectable at room temperature and gelled in situ at body temperature. Particularly, the liraglutide-loaded PCGA-PEG-PCGA thermogel formulation exhibited a sustained drug release manner over one week in both in vitro and in vivo tests. This feature was attributed to the combined effects of an appropriate drug/polymer interaction and a high chain mobility of the carrier polymer, which facilitated the sustained diffusion of drug out of the thermogel. Finally, a single subcutaneous injection of this formulation showed a remarkably improved glucose tolerance of mice for one week. Hence, the present study not only developed a promising long-acting antidiabetic formulation, but also put forward a combined strategy for controlled delivery of polypeptide.
authors.affiliation: State Key Laboratory of Molecular Engineering of Polymers, Collaborative Innovation Center of Polymers and Polymer Composite Materials, Department of Macromolecular Science, Fudan University, Shanghai, 200433, China.
authors.forename: Yipei
authors.initials: Y
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Molecular Engineering of Polymers, Collaborative Innovation Center of Polymers and Polymer Composite Materials, Department of Macromolecular Science, Fudan University, Shanghai, 200433, China.
authors.forename: Yuzhuo
authors.initials: Y
authors.lastname: Li
authors.affiliation: State Key Laboratory of Molecular Engineering of Polymers, Collaborative Innovation Center of Polymers and Polymer Composite Materials, Department of Macromolecular Science, Fudan University, Shanghai, 200433, China.
authors.forename: Wenjia
authors.initials: W
authors.lastname: Shen
authors.affiliation: National Pharmaceutical Engineering Research Center, China State Institute of Pharmaceutical Industry, Shanghai, 200437, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Li
authors.affiliation: State Key Laboratory of Molecular Engineering of Polymers, Collaborative Innovation Center of Polymers and Polymer Composite Materials, Department of Macromolecular Science, Fudan University, Shanghai, 200433, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Yu
authors.affiliation: National Pharmaceutical Engineering Research Center, China State Institute of Pharmaceutical Industry, Shanghai, 200437, China.
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Molecular Engineering of Polymers, Collaborative Innovation Center of Polymers and Polymer Composite Materials, Department of Macromolecular Science, Fudan University, Shanghai, 200433, China.
authors.forename: Jiandong
authors.initials: J
authors.lastname: Ding
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D005782:Gels; D005951:Glucose Tolerance Test; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D000069450:Liraglutide / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D051379:Mice; D008813:Mice, Inbred ICR; D011108:Polymers / Q000008:administration & dosage*
chemical_list: D001786:Blood Glucose; D005782:Gels; D007004:Hypoglycemic Agents; D011108:Polymers; D000069450:Liraglutide