Injectable sustained-release hydrogel for high-concentration antibody delivery
There is an increasing interest in subcutaneous (SC) delivery as an alternative to the traditional intravenous (IV) for immunotherapies and other advanced therapies. High-concentration formulations of antibodies are needed to meet the limited-volume requirements of subcutaneous SC delivery. Despite...
| Main Authors: | , |
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| Other Authors: | |
| Format: | Article |
| Language: | English |
| Published: |
Royal Society of Chemistry
2025
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| Online Access: | https://hdl.handle.net/1721.1/158252 |
| _version_ | 1826194368625639424 |
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| author | Zheng, Talia Doyle, Patrick S |
| author2 | Massachusetts Institute of Technology. Department of Chemical Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Chemical Engineering Zheng, Talia Doyle, Patrick S |
| author_sort | Zheng, Talia |
| collection | MIT |
| description | There is an increasing interest in subcutaneous (SC) delivery as an alternative to the traditional intravenous (IV) for immunotherapies and other advanced therapies. High-concentration formulations of antibodies are needed to meet the limited-volume requirements of subcutaneous SC delivery. Despite this need, there remain challenges in delivering stable and injectable antibodies in these high concentrations. Hydrogel encapsulation of amorphous solid antibodies has been proven to improve the stability and injectability of high-concentration antibody formulations. However, the antibody is quickly released from the hydrogel due to the material's porosity, leading to rapid, uncontrolled drug release kinetics undesirable for the drug's efficacy and safety. In this paper, we propose a dual-network composite hydrogel which leverages interactions between the two polymer networks to achieve controlled release of the antibody. We load the solid form of the antibody at high concentrations within alginate hydrogel microparticles which are then suspended in thermogelling methylcellulose solution to formulate the in situ gelling composite hydrogel. By facile chemical modification of the alginate to tune the microparticles’ gel properties and alginate–methylcellulose interactions, we demonstrate how the composite system can delay release of the drug in a tunable manner and achieve a near-zero order release profile for improved therapeutic efficacy. We show acceptable injectability properties of the composite hydrogel at high antibody concentrations, highlighting the functionalities of dualnetwork encapsulation. We imagine this composite system to be applicable for the sustained delivery of various therapeutic protein forms, especially for high-loading SC formulations. |
| first_indexed | 2025-03-10T08:17:46Z |
| format | Article |
| id | mit-1721.1/158252 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2025-03-10T08:17:46Z |
| publishDate | 2025 |
| publisher | Royal Society of Chemistry |
| record_format | dspace |
| spelling | mit-1721.1/1582522025-02-24T19:32:20Z Injectable sustained-release hydrogel for high-concentration antibody delivery Zheng, Talia Doyle, Patrick S Massachusetts Institute of Technology. Department of Chemical Engineering There is an increasing interest in subcutaneous (SC) delivery as an alternative to the traditional intravenous (IV) for immunotherapies and other advanced therapies. High-concentration formulations of antibodies are needed to meet the limited-volume requirements of subcutaneous SC delivery. Despite this need, there remain challenges in delivering stable and injectable antibodies in these high concentrations. Hydrogel encapsulation of amorphous solid antibodies has been proven to improve the stability and injectability of high-concentration antibody formulations. However, the antibody is quickly released from the hydrogel due to the material's porosity, leading to rapid, uncontrolled drug release kinetics undesirable for the drug's efficacy and safety. In this paper, we propose a dual-network composite hydrogel which leverages interactions between the two polymer networks to achieve controlled release of the antibody. We load the solid form of the antibody at high concentrations within alginate hydrogel microparticles which are then suspended in thermogelling methylcellulose solution to formulate the in situ gelling composite hydrogel. By facile chemical modification of the alginate to tune the microparticles’ gel properties and alginate–methylcellulose interactions, we demonstrate how the composite system can delay release of the drug in a tunable manner and achieve a near-zero order release profile for improved therapeutic efficacy. We show acceptable injectability properties of the composite hydrogel at high antibody concentrations, highlighting the functionalities of dualnetwork encapsulation. We imagine this composite system to be applicable for the sustained delivery of various therapeutic protein forms, especially for high-loading SC formulations. 2025-02-24T19:32:19Z 2025-02-24T19:32:19Z 2025-01-21 2025-02-24T19:20:56Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/158252 Zheng, Talia and Doyle, Patrick S. 2025. "Injectable sustained-release hydrogel for high-concentration antibody delivery." RSC Pharmaceutics, 2 (1). en 10.1039/d4pm00290c RSC Pharmaceutics Creative Commons Attribution-Noncommercial-ShareAlike http://creativecommons.org/licenses/by-nc/4.0/ application/pdf Royal Society of Chemistry Royal Society of Chemistry |
| spellingShingle | Zheng, Talia Doyle, Patrick S Injectable sustained-release hydrogel for high-concentration antibody delivery |
| title | Injectable sustained-release hydrogel for high-concentration antibody delivery |
| title_full | Injectable sustained-release hydrogel for high-concentration antibody delivery |
| title_fullStr | Injectable sustained-release hydrogel for high-concentration antibody delivery |
| title_full_unstemmed | Injectable sustained-release hydrogel for high-concentration antibody delivery |
| title_short | Injectable sustained-release hydrogel for high-concentration antibody delivery |
| title_sort | injectable sustained release hydrogel for high concentration antibody delivery |
| url | https://hdl.handle.net/1721.1/158252 |
| work_keys_str_mv | AT zhengtalia injectablesustainedreleasehydrogelforhighconcentrationantibodydelivery AT doylepatricks injectablesustainedreleasehydrogelforhighconcentrationantibodydelivery |