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

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