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Journal article
Sustained release of drug-loaded nanoparticles from injectable hydrogels enables long-term control of macrophage phenotype
Biomaterials science, v 10(24), pp 6951-6967
07 Nov 2022
PMID: 36341688
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Injectable hydrogels may be pre-formed through dynamic crosslinks, allowing for injection and subsequent retention in the tissue by shear-thinning and self-healing processes, respectively. These properties enable the site-specific delivery of encapsulated therapeutics; yet, the sustained release of small-molecule drugs and their cell-targeted delivery remains challenging due to their rapid diffusive release and non-specific cellular biodistribution. Herein, we develop an injectable hydrogel system composed of a macrophage-targeted nanoparticle (cyclodextrin nanoparticles, CDNPs) crosslinked by adamantane-modified hyaluronic acid (Ad-HA). The polymer-nanoparticle hydrogel uniquely leverages cyclodextrin's interaction with small molecule drugs to create a spatially discrete drug reservoir and with adamantane to yield dynamic, injectable hydrogels. Through an innovative two-step drug screening approach and examination of 45 immunomodulatory drugs with subsequent in-depth transcriptional profiling of both murine and human macrophages, we identify celastrol as a potent inhibitor of pro-inflammatory (M1-like) behavior that furthermore promotes a reparatory (M2-like) phenotype. Celastrol encapsulation within the polymer-nanoparticle hydrogels permitted shear-thinning injection and sustained release of drug-laden nanoparticles that targeted macrophages to modulate cell behavior for greater than two weeks in vitro. The modular hydrogel system is a promising approach to locally modulate cell-specific phenotype in a range of applications for immunoregenerative medicine.
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Details
- Title
- Sustained release of drug-loaded nanoparticles from injectable hydrogels enables long-term control of macrophage phenotype
- Creators
- Shreya S Soni - Drexel UniversityArielle M D'Elia - Drexel UniversityAbdulrahman Alsasa - Drexel UniversitySylvia Cho - Drexel UniversityTina Tylek - Drexel UniversityErin M O'Brien - Drexel UniversityRicardo Whitaker - Drexel UniversityKara L Spiller - Drexel UniversityChristopher B Rodell - Drexel University
- Publication Details
- Biomaterials science, v 10(24), pp 6951-6967
- Publisher
- Royal Society of Chemistry
- Number of pages
- 17
- Grant note
- R35GM147184; R01HL130037 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA Startup Funds from the School of Biomedical Engineering, Science and Health Systems at Drexel University
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems
- Web of Science ID
- WOS:000880760800001
- Scopus ID
- 2-s2.0-85142331623
- Other Identifier
- 991019280037404721
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InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Web of Science research areas
- Materials Science, Biomaterials