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Journal article
Injectable Granular Hydrogels Enable Avidity-Controlled Biotherapeutic Delivery
ACS biomaterials science & engineering, v 10(3), pp 1577-1588
11 Mar 2024
PMID: 38357739
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Protein therapeutics represent a rapidly growing class of pharmaceutical agents that hold great promise for the treatment of various diseases such as cancer and autoimmune dysfunction. Conventional systemic delivery approaches, however, result in off-target drug exposure and a short therapeutic half-life, highlighting the need for more localized and controlled delivery. We have developed an affinity-based protein delivery system that uses guest-host complexation between β-cyclodextrin (CD, host) and adamantane (Ad, guest) to enable sustained localized biomolecule presentation. Hydrogels were formed by the copolymerization of methacrylated CD and methacrylated dextran. Extrusion fragmentation of bulk hydrogels yielded shear-thinning and self-healing granular hydrogels (particle diameter = 32.4 ± 16.4 μm) suitable for minimally invasive delivery and with a high host capacity for the retention of guest-modified proteins. Bovine serum albumin (BSA) was controllably conjugated to Ad via EDC chemistry without affecting the affinity of the Ad moiety for CD (= 12.0 ± 1.81 μM; isothermal titration calorimetry). The avidity of Ad-BSA conjugates was directly tunable through the number of guest groups attached, resulting in a fourfold increase in the complex half-life (= 5.07 ± 1.23 h, surface plasmon resonance) that enabled a fivefold reduction in protein release at 28 days. Furthermore, we demonstrated that the conjugation of Ad to immunomodulatory cytokines (IL-4, IL-10, and IFNγ) did not detrimentally affect cytokine bioactivity and enabled their sustained release. Our strategy of avidity-controlled delivery of protein-based therapeutics is a promising approach for the sustained local presentation of protein therapeutics and can be applied to numerous biomedical applications.
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Details
- Title
- Injectable Granular Hydrogels Enable Avidity-Controlled Biotherapeutic Delivery
- Creators
- Arielle M D'Elia - Drexel University, School of Biomedical Engineering, Science, and Health SystemsOlivia L Jones - School of Biomedical Engineering, Science and Health Systems, Drexel University, Philadelphia, Pennsylvania 19104, United StatesGabriela Canziani - Drexel University, Biochemistry and Molecular BiologyBiplab Sarkar - Drexel UniversityIrwin Chaiken - Drexel University, Biochemistry and Molecular BiologyChristopher B Rodell - Drexel University, School of Biomedical Engineering, Science, and Health Systems
- Publication Details
- ACS biomaterials science & engineering, v 10(3), pp 1577-1588
- Publisher
- American Chemical Society (ACS)
- Number of pages
- 12
- Grant note
- R35 GM147184 / NIGMS NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biochemistry and Molecular Biology; School of Biomedical Engineering, Science, and Health Systems
- Web of Science ID
- WOS:001164675100001
- Scopus ID
- 2-s2.0-85185574039
- Other Identifier
- 991021853435604721
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InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Web of Science research areas
- Materials Science, Biomaterials