Unveiling the Rational Development of Stimuli-Responsive Silk Fibroin-Based Ionogel Formulations

Article


Shmool, T. A., Martin, L. K., Jirkas, A., Matthews, R. P., Constantinou, A. P., Vadukul, D. M., Georgiou, T. K., Aprile, F. A. and Hallett, J. P. 2023. Unveiling the Rational Development of Stimuli-Responsive Silk Fibroin-Based Ionogel Formulations. Chemistry of Materials. 35 (15), p. 5798–5808. https://doi.org/10.1021/acs.chemmater.3c00303
AuthorsShmool, T. A., Martin, L. K., Jirkas, A., Matthews, R. P., Constantinou, A. P., Vadukul, D. M., Georgiou, T. K., Aprile, F. A. and Hallett, J. P.
Abstract

We present an approach for the rational development of stimuli-responsive ionogels which can be formulated for precise control of multiple unique ionogel features and fill niche pharmaceutical applications. Ionogels are captivating materials, exhibiting self-healing characteristics, tunable mechanical and structural properties, high thermal stability, and electroconductivity. However, the majority of ionogels developed require complex chemistry, exhibit high viscosity, poor biocompatibility, and low biodegradability. In our work, we overcome these limitations. We employ a facile production process and strategically integrate silk fibroin, the biocompatible ionic liquids (ILs) choline acetate ([Cho][OAc]), choline dihydrogen phosphate ([Cho][DHP]), and choline chloride ([Cho][Cl]), traditional pharmaceutical excipients, and the model antiepileptic drug phenobarbital. In the absence of ILs, we failed to observe gel formation; yet in the presence of ILs, thermoresponsive ionogels formed. Systems were assessed via visual tests, transmission electron microscopy, confocal reflection microscopy, dynamic light scattering, zeta potential and rheology measurements. We formed diverse ionogels of strengths ranging between 18 and 642 Pa. Under 25 °C storage, formulations containing polyvinylpyrrolidone (PVP) showed an ionogel formation period ranging over 14 days, increasing in the order of [Cho][DHP], [Cho][OAc], and [Cho][Cl]. Formulations lacking PVP showed an ionogel formation period ranging over 32 days, increasing in the order of [Cho][OAc], [Cho][DHP] and [Cho][Cl]. By heating from 25 to 60 °C, immediately following preparation, thermoresponsive ionogels formed below 41 °C in the absence of PVP. Based on our experimental results and density functional theory calculations, we attribute ionogel formation to macromolecular crowding and confinement effects, further enhanced upon PVP inclusion. Holistically, applying our rational development strategy enables the production of ionogels of tunable physicochemical and rheological properties, enhanced drug solubility, and structural and energetic stability. We believe our rational development approach will advance the design of biomaterials and smart platforms for diverse drug delivery applications.

JournalChemistry of Materials
Journal citation35 (15), p. 5798–5808
ISSN0897-4756
Year2023
PublisherAmerican Chemical Society (ACS)
Publisher's version
License
File Access Level
Anyone
Digital Object Identifier (DOI)https://doi.org/10.1021/acs.chemmater.3c00303
Publication dates
Online20 Jul 2023
Print08 Aug 2023
Publication process dates
Deposited30 Oct 2023
FunderDepartment of Health and Social Care
Engineering and Physical Sciences Research Council (EPSRC)
UKRI
Alzheimer’s Research UK
Copyright holder© 2023, The Authors
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