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Journal article
Sustained small molecule delivery from injectable hyaluronic acid hydrogels through host-guest mediated retention
Journal of materials chemistry. B, Materials for biology and medicine, v 3(40), pp 8010-8019
01 Jan 2015
PMID: 26693019
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Self-assembled and injectable hydrogels have many beneficial properties for the local delivery of therapeutics; however, challenges still exist in the sustained release of small molecules from these highly hydrated networks. Host-guest chemistry between beta-cyclodextrin (CD) and adamantane has been used to create supramolecular hydrogels from modified polymers. Beyond assembly, this chemistry may also provide increased drug retention and sustained release through the formation of inclusion complexes between drugs and CD. Here, we engineered a two-component system from adamantane-modified and CD-modified hyaluronic acid (HA), a natural component of the extracellular matrix, to produce hydrogels that are both injectable and able to sustain the release of small molecules. The conjugation of CD to HA dramatically altered its affinity for hydrophobic small molecules, such as tryptophan. This interaction led to lower molecule diffusivity and the release of small molecules for up to 21 days with release profiles dependent on CD concentration and drug-CD affinity. There was significant attenuation of release from the supramolecular hydrogels (similar to 20% release in 24 h) when compared to hydrogels without CD (similar to 90% release in 24 h). The loading of small molecules also had no effect on hydrogel mechanics or self-assembly properties. Finally, to illustrate this controlled delivery approach with clinically used small molecule pharmaceuticals, we sustained the release of two widely used drugs (i.e., doxycycline and doxorubicin) from these hydrogels.
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Details
- Title
- Sustained small molecule delivery from injectable hyaluronic acid hydrogels through host-guest mediated retention
- Creators
- Joshua E. Mealy - University of PennsylvaniaChristopher B. Rodell - University of PennsylvaniaJason A. Burdick - University of Pennsylvania
- Publication Details
- Journal of materials chemistry. B, Materials for biology and medicine, v 3(40), pp 8010-8019
- Publisher
- Royal Soc Chemistry
- Number of pages
- 10
- Grant note
- R01HL107938 / NATIONAL HEART, LUNG, AND BLOOD INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) American Heart Association National Science Foundation; National Science Foundation (NSF) R01 HL111090; R01 HL107938 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems
- Web of Science ID
- WOS:000362663000020
- Scopus ID
- 2-s2.0-84943601749
- Other Identifier
- 991019176803304721
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InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Web of Science research areas
- Materials Science, Biomaterials