{"@context":{"@vocab":"https://cir.nii.ac.jp/schema/1.0/","rdfs":"http://www.w3.org/2000/01/rdf-schema#","dc":"http://purl.org/dc/elements/1.1/","dcterms":"http://purl.org/dc/terms/","foaf":"http://xmlns.com/foaf/0.1/","prism":"http://prismstandard.org/namespaces/basic/2.0/","cinii":"http://ci.nii.ac.jp/ns/1.0/","datacite":"https://schema.datacite.org/meta/kernel-4/","ndl":"http://ndl.go.jp/dcndl/terms/","jpcoar":"https://github.com/JPCOAR/schema/blob/master/2.0/"},"@id":"https://cir.nii.ac.jp/crid/1361699994876548992.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.1073/pnas.1215498110"}},{"identifier":{"@type":"URI","@value":"https://pnas.org/doi/pdf/10.1073/pnas.1215498110"}}],"dc:title":[{"@value":"Hydrogel drug delivery system with predictable and tunable drug release and degradation rates"}],"description":[{"type":"abstract","notation":[{"@value":"<jats:p>Many drugs and drug candidates are suboptimal because of short duration of action. For example, peptides and proteins often have serum half-lives of only minutes to hours. One solution to this problem involves conjugation to circulating carriers, such as PEG, that retard kidney filtration and hence increase plasma half-life of the attached drug. We recently reported an approach to half-life extension that uses sets of self-cleaving linkers to attach drugs to macromolecular carriers. The linkers undergo β-eliminative cleavage to release the native drug with predictable half-lives ranging from a few hours to over 1 y; however, half-life extension becomes limited by the renal elimination rate of the circulating carrier. An approach to overcoming this constraint is to use noncirculating, biodegradable s.c. implants as drug carriers that are stable throughout the duration of drug release. Here, we use β-eliminative linkers to both tether drugs to and cross-link PEG hydrogels, and demonstrate tunable drug release and hydrogel erosion rates over a very wide range. By using one β-eliminative linker to tether a drug to the hydrogel, and another β-eliminative linker with a longer half-life to control polymer degradation, the system can be coordinated to release the drug before the gel undergoes complete erosion. The practical utility is illustrated by a PEG hydrogel–exenatide conjugate that should allow once-a-month administration, and results indicate that the technology may serve as a generic platform for tunable ultralong half-life extension of potent therapeutics.</jats:p>"}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1380576198347031297","@type":"Researcher","foaf:name":[{"@value":"Gary W. Ashley"}],"jpcoar:affiliationName":[{"@value":"ProLynx, San Francisco, CA 94158"}]},{"@id":"https://cir.nii.ac.jp/crid/1380576198347031296","@type":"Researcher","foaf:name":[{"@value":"Jeff Henise"}],"jpcoar:affiliationName":[{"@value":"ProLynx, San Francisco, CA 94158"}]},{"@id":"https://cir.nii.ac.jp/crid/1380576198347031299","@type":"Researcher","foaf:name":[{"@value":"Ralph Reid"}],"jpcoar:affiliationName":[{"@value":"ProLynx, San Francisco, CA 94158"}]},{"@id":"https://cir.nii.ac.jp/crid/1380576198347031298","@type":"Researcher","foaf:name":[{"@value":"Daniel V. Santi"}],"jpcoar:affiliationName":[{"@value":"ProLynx, San Francisco, CA 94158"}]}],"publication":{"publicationIdentifier":[{"@type":"PISSN","@value":"00278424"},{"@type":"EISSN","@value":"10916490"}],"prism:publicationName":[{"@value":"Proceedings of the National Academy of Sciences"}],"dc:publisher":[{"@value":"Proceedings of the National Academy of Sciences"}],"prism:publicationDate":"2013-01-23","prism:volume":"110","prism:number":"6","prism:startingPage":"2318","prism:endingPage":"2323"},"reviewed":"false","url":[{"@id":"https://pnas.org/doi/pdf/10.1073/pnas.1215498110"}],"createdAt":"2013-01-24","modifiedAt":"2022-04-13","relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1360004229910914304","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Non‐Osmotic Hydrogels: A Rational Strategy for Safely Degradable Hydrogels"}]},{"@id":"https://cir.nii.ac.jp/crid/1360017280641263360","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Polyampholyte‐Based Polymer Hydrogels for the Long‐Term Storage, Protection and Delivery of Therapeutic Proteins"}]},{"@id":"https://cir.nii.ac.jp/crid/1360285704856289792","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Tough Hydrogels with Fast, Strong, and Reversible Underwater Adhesion Based on a Multiscale Design"}]},{"@id":"https://cir.nii.ac.jp/crid/1360580230577907712","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Highly Processable Covalent Organic Framework Gel Electrolyte Enabled by Side‐Chain Engineering for Lithium‐Ion Batteries"}]}],"dataSourceIdentifier":[{"@type":"CROSSREF","@value":"10.1073/pnas.1215498110"},{"@type":"CROSSREF","@value":"10.1002/ange.201602610_references_DOI_RMRVo3F8NeRpAu59B3beEeMD8Me"},{"@type":"CROSSREF","@value":"10.1002/adhm.202203253_references_DOI_RMRVo3F8NeRpAu59B3beEeMD8Me"},{"@type":"CROSSREF","@value":"10.1002/adma.201801884_references_DOI_RMRVo3F8NeRpAu59B3beEeMD8Me"},{"@type":"CROSSREF","@value":"10.1002/anie.201602610_references_DOI_RMRVo3F8NeRpAu59B3beEeMD8Me"},{"@type":"CROSSREF","@value":"10.1002/ange.202110695_references_DOI_RMRVo3F8NeRpAu59B3beEeMD8Me"}]}