Oral delivery of exenatide via microspheres prepared by cross-linking of alginate and hyaluronate.
Exenatide is an FDA-approved glucose-lowering peptide drug for the treatment of type 2 diabetes by subcutaneous injection. To address the issues on the inconvenience for patient use and the difficulty of oral administration of peptide drugs, chemical cross-linking of two pH-responsive biomaterials, alginate and hyaluronate, was carried out to prepare a new material for the encapsulation of exenatide as a form of microspheres. The exenatide-loaded microspheres exhibited spherical structures with excellent loading and release behaviors in the simulated gastrointestinal tract environments. After oral administration of the microspheres in db/db mice, maximum plasma concentration of exenatide appeared at 4 hours, and blood glucose was effectively reduced to a normal level within 2 hours and maintained for another 4 hours. The bioavailability of the exenatide-loaded microspheres, relative to subcutaneous injection of exenatide, reached 10.2%. Collectively, the present study demonstrated the feasibility of orally delivering exenatide with the new cross-linked biomaterial and formulation, and showed therapeutic potential for clinical applications.
State Key Laboratory of Natural Medicines and Laboratory of Chemical Biology, China Pharmaceutical University, Nanjing, China.
Baojie
B
Zhang
State Key Laboratory of Natural Medicines and Laboratory of Chemical Biology, China Pharmaceutical University, Nanjing, China.
Dongyang
D
He
State Key Laboratory of Natural Medicines and Laboratory of Chemical Biology, China Pharmaceutical University, Nanjing, China.
Yu
Y
Fan
State Key Laboratory of Natural Medicines and Laboratory of Chemical Biology, China Pharmaceutical University, Nanjing, China.
Nan
N
Liu
State Key Laboratory of Natural Medicines and Laboratory of Chemical Biology, China Pharmaceutical University, Nanjing, China.
Yijun
Y
Chen
D000284:Administration, Oral; D000464:Alginates / Q000737:chemistry*; D000818:Animals; D002849:Chromatography, Gas; D003432:Cross-Linking Reagents / Q000737:chemistry*; D016503:Drug Delivery Systems; D000077270:Exenatide; D020723:Glucuronic Acid / Q000737:chemistry; D005976:Glutaral / Q000032:analysis; D006603:Hexuronic Acids / Q000737:chemistry; D006820:Hyaluronic Acid / Q000737:chemistry*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D008970:Molecular Weight; D010455:Peptides / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology*; D013501:Surface-Active Agents / Q000737:chemistry; D014688:Venoms / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology*
D000464:Alginates; D003432:Cross-Linking Reagents; D006603:Hexuronic Acids; D010455:Peptides; D013501:Surface-Active Agents; D014688:Venoms; D020723:Glucuronic Acid; D006820:Hyaluronic Acid; D000077270:Exenatide; D005976:Glutaral