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Mechanistic investigations into the encapsulation and release of small molecules and proteins from a supramolecular nucleoside gel in vitro and in vivo

Faidra Angelerou, Maria Galini; Markus, Robert; Paraskevopoulou, Vasiliki; Foralosso, Rugerro; Clarke, Philip; Alvarez, Clara V.; Chenlo, Miguel; Johnson, Litty; Rutland, Catrin; Allen, Stephanie; Brasnett, Christopher; Seddon, Annela; Zelzer, Mischa; Marlow, Maria

Mechanistic investigations into the encapsulation and release of small molecules and proteins from a supramolecular nucleoside gel in vitro and in vivo Thumbnail


Authors

Maria Galini Faidra Angelerou

Robert Markus

Vasiliki Paraskevopoulou

Rugerro Foralosso

Philip Clarke

Clara V. Alvarez

Miguel Chenlo

Litty Johnson

CATRIN RUTLAND CATRIN.RUTLAND@NOTTINGHAM.AC.UK
Professor of Molecular Medicine

Stephanie Allen

Christopher Brasnett

Annela Seddon



Abstract

Supramolecular gels have recently emerged as promising biomaterials for the delivery of a wide range of bioactive molecules, from small hydrophobic drugs to large biomolecules such as proteins. Although it has been demonstrated that each encapsulated molecule has a different release profile from the hydrogel, so far diffusion and steric impediment have been identified as the only mechanisms for the release of molecules from supramolecular gels. Erosion of a supramolecular gel has not yet been reported to contribute to the release profiles of encapsulated molecules. Here, we use a novel nucleoside-based supramolecular gel as a drug delivery system for proteins with different properties and a hydrophobic dye and describe for the first time how these materials interact, encapsulate and eventually release bioactive molecules through an erosion-based process. Through fluorescence microscopy and spectroscopy as well as Small Angle X-ray scattering, we show that the encapsulated molecules directly interact with the hydrogel fibres - rather than being physically entrapped in the gel network. The ability of these materials to protect proteins against enzymatic degradation is also demonstrated here for the first time. In addition, the released proteins were proven to be functional in vitro. Real-time fluorescence microscopy together with macroscopic release studies confirm that erosion is the key release mechanism. In vivo, the gel completely degrades after two weeks and no signs of inflammation are detected, demonstrating its in vivo safety. By establishing the contribution of erosion as a key driving force behind the release of bioactive molecules from supramolecular gels, this work provides mechanistic insight into the way molecules with different properties are encapsulated and released from a nucleoside-based supramolecular gel and sets the basis for the design of more tailored supramolecular gels for drug delivery applications.

Citation

Faidra Angelerou, M. G., Markus, R., Paraskevopoulou, V., Foralosso, R., Clarke, P., Alvarez, C. V., …Marlow, M. (2020). Mechanistic investigations into the encapsulation and release of small molecules and proteins from a supramolecular nucleoside gel in vitro and in vivo. Journal of Controlled Release, 317, 118-129. https://doi.org/10.1016/j.jconrel.2019.10.011

Journal Article Type Article
Acceptance Date Oct 2, 2019
Online Publication Date Oct 31, 2019
Publication Date Jan 10, 2020
Deposit Date Nov 6, 2019
Publicly Available Date Dec 4, 2019
Journal Journal of Controlled Release
Print ISSN 0168-3659
Electronic ISSN 1873-4995
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 317
Pages 118-129
DOI https://doi.org/10.1016/j.jconrel.2019.10.011
Keywords Pharmaceutical Science
Public URL https://nottingham-repository.worktribe.com/output/3067575
Publisher URL https://www.sciencedirect.com/science/article/pii/S0168365919305681?via%3Dihub
Contract Date Nov 6, 2019

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