title: Sol-gel transition of nanoparticles/polymer mixtures for sustained delivery of exenatide to treat type 2 diabetes mellitus.
abstract: The sol-gel transition of nanoparticles (NPs)/polymer mixture in aqueous medium was investigated for the sustained delivery of exenatide to treat type 2 diabetes mellitus. Exenatide-loaded multilayer NPs were prepared using a layer-by-layer approach which utilized the interaction between Pluronics and lipid bilayers as the main driving force for the construction of the multilayer. Pluronic F-127 was the polymer used, and it forms a gel at body temperature. Although the antidiabetic effects of exenatide-loaded multilayer NPs have been demonstrated previously in an animal model, in this work, the attempt was made to demonstrate the extended duration of antidiabetic effects, which was accomplished by localizing the exenatide-loaded NPs in muscular areas in the body through the gelation of Pluronic F-127. Transmittance electron microscopy and dynamic light scattering were used to examine the morphology of the multilayer NPs/polymer mixture. A change in the release pattern of exenatide was observed after gel formation at body temperature, and Sodium Dodecyl Sulfate-Polyacrylamide Gel Electrophoresis was performed using native exenatide and a reference biomarker as control to observe whether exenatide extracted from the multilayer NPs and the multilayer NPs/Pluronic F-127 mixture degraded or not. We then observed the antidiabetic effect of exenatide-loaded multilayer NPs/Pluronic F-127 mixture by monitoring blood-glucose levels in db/db mice. In vitro and in vivo correlation was discussed regarding structural variation in the delivery vehicles.
authors.affiliation: College of Pharmacy, Korea University, Sejong, Republic of Korea.
authors.forename: Keun Sang
authors.initials: KS
authors.lastname: Oh
authors.affiliation: College of Pharmacy, Korea University, Sejong, Republic of Korea.
authors.forename: Jae Yeon
authors.initials: JY
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Korea University, Sejong, Republic of Korea.
authors.forename: Byeong Deok
authors.initials: BD
authors.lastname: Yoon
authors.affiliation: College of Pharmacy, Korea University, Sejong, Republic of Korea.
authors.forename: Minae
authors.initials: M
authors.lastname: Lee
authors.affiliation: College of Pharmacy, Korea University, Sejong, Republic of Korea; Department of Physiology, McGill University, Montreal, Canada.
authors.forename: Heejoo
authors.initials: H
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Korea University, Sejong, Republic of Korea; Department of Biology, University of Washington, Seattle, USA.
authors.forename: Michelle
authors.initials: M
authors.lastname: Kim
authors.affiliation: Biomedical Research Center, Korea University Guro Hospital, Seoul, Republic of Korea.
authors.forename: Jae Hong
authors.initials: JH
authors.lastname: Seo
authors.affiliation: College of Pharmacy, Korea University, Sejong, Republic of Korea; Biomedical Research Center, Korea University Guro Hospital, Seoul, Republic of Korea. Electronic address: shyuk@korea.ac.kr.
authors.forename: Soon Hong
authors.initials: SH
authors.lastname: Yuk
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D003692:Delayed-Action Preparations; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004337:Drug Carriers / Q000737:chemistry*; D065546:Drug Liberation; D004591:Electrophoresis, Polyacrylamide Gel; D000077270:Exenatide; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D007279:Injections, Subcutaneous; D008297:Male; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D010455:Peptides / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D044367:Phase Transition; D020442:Poloxamer / Q000737:chemistry*; D013499:Surface Properties; D014688:Venoms / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use
chemical_list: D001786:Blood Glucose; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D007004:Hypoglycemic Agents; D010455:Peptides; D014688:Venoms; D020442:Poloxamer; D000077270:Exenatide
keywords: Exenatide; Nanoparticles/polymer mixture; Pluronics; Sol–gel transition; Sustained delivery; Type 2 diabetes mellitus