title: Microstructured dextran hydrogels for burst-free sustained release of PEGylated protein drugs.
abstract: Hydrogels have gained significant attention as ideal delivery vehicles for protein drugs. However, the use of hydrogels for protein delivery has been restricted because their porous structures inevitably cause a premature leakage of encapsulated proteins. Here, we report a simple yet effective approach to regulate the protein release kinetics of hydrogels through the creation of microstructures, which serve as a reservoir, releasing their payloads in a controlled manner. Microstructured dextran hydrogels enable burst-free sustained release of PEGylated interferon over 3 months without compromising its bioactivity. These hydrogels substantially extend the circulation half-life of PEGylated interferon, allowing for less frequent dosing in a humanized mouse model of hepatitis C. The present approach opens up possibilities for the development of sustained protein delivery systems for a broad range of pharmaceutical and biomedical applications.
authors.affiliation: Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, The Nanos, Singapore 138669, Singapore.
authors.forename: Ki Hyun
authors.initials: KH
authors.lastname: Bae
authors.affiliation: Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, The Nanos, Singapore 138669, Singapore.
authors.forename: Fan
authors.initials: F
authors.lastname: Lee
authors.affiliation: Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, The Nanos, Singapore 138669, Singapore.
authors.forename: Keming
authors.initials: K
authors.lastname: Xu
authors.affiliation: Institute of Molecular and Cell Biology, 61 Biopolis Drive, The Proteos, Singapore 138673, Singapore.
authors.forename: Choong Tat
authors.initials: CT
authors.lastname: Keng
authors.affiliation: Institute of Molecular and Cell Biology, 61 Biopolis Drive, The Proteos, Singapore 138673, Singapore.
authors.forename: Sue Yee
authors.initials: SY
authors.lastname: Tan
authors.affiliation: Institute of Molecular and Cell Biology, 61 Biopolis Drive, The Proteos, Singapore 138673, Singapore; Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore.
authors.forename: Yee Joo
authors.initials: YJ
authors.lastname: Tan
authors.affiliation: Institute of Molecular and Cell Biology, 61 Biopolis Drive, The Proteos, Singapore 138673, Singapore; Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore; Interdisciplinary Research Group in Infectious Diseases, Singapore-Massachusetts Institute of Technology Alliance for Research and Technology, Singapore 138602, Singapore. Electronic address: qchen@imcb.a-star.edu.sg.
authors.forename: Qingfeng
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, The Nanos, Singapore 138669, Singapore. Electronic address: mkurisawa@ibn.a-star.edu.sg.
authors.forename: Motoichi
authors.initials: M
authors.lastname: Kurisawa
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D045744:Cell Line, Tumor; D003692:Delayed-Action Preparations / Q000737:chemistry*; D003911:Dextrans / Q000737:chemistry*; D016174:Hepacivirus / Q000187:drug effects / Q000302:isolation & purification; D006526:Hepatitis C / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D020100:Hydrogels / Q000737:chemistry*; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D008099:Liver / Q000473:pathology / Q000821:virology*; D008297:Male; D051379:Mice; D011092:Polyethylene Glycols / Q000737:chemistry
chemical_list: D000998:Antiviral Agents; D003692:Delayed-Action Preparations; D003911:Dextrans; D020100:Hydrogels; D016898:Interferon-alpha; D011092:Polyethylene Glycols
keywords: Controlled drug release; Dextran; Hydrogels; Microstructure; Protein