Next generation strategy for tuning the thermoresponsive properties of micellar and hydrogel drug delivery vehicles using ionic liquids

Shmool, Talia A.; Constantinou, Anna P.; Jirkas, Andreas; Zhao, Chen; Georgiou, Theoni K.; Hallett, Jason P.

doi:10.1039/d2py00053a

Cited by 6 publications

(26 citation statements)

References 57 publications

(144 reference statements)

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“… 14 Together, the chloride anions can contribute to enhanced structural stability against collapse by electrostatic interactions, 14 , 15 forming a viscoelastic interfacial stabilization network hindering changes in the protein structure, adsorption at the air–water interface, and increase in dynamic surface tension. 16 , 61 − 63 Furthermore, the observed Y-shaped conformer adopted in 30 and 50 wt % at 25 °C suggests dampening of the dynamics for these systems, possibly due to preferential interactions of IgG4 with [Cho]Cl in concentrated solutions. From this, we infer that water is excluded from the vicinity of the protein surface, also supported by the highest Γ 23 values observed for water.…”

Section: Discussionmentioning

confidence: 95%

“…For the experimental measurements performed, these conditions were previously found optimum. 14 − 16 For each solution, IgG4 concentration was confirmed by measurements on the NanoDrop One ThermoFischer Scientific Inc. (Thermo Fisher Scientific Inc., Waltham, MA USA).…”

Section: Methodsmentioning

confidence: 99%

“…The pH of each solution was measured using the pH electrode Mettler Toledo InLab Micro (WOLFLABS, Pocklington, York, UK). As previously described, 16 to investigate the change in D h and PDI, DLS measurements were performed using a Zetasizer Nano ZS (Malvern Panalytical Ltd., Malvern, UK) at a 90° scattering angle; and to determine the surface charge, zeta potential measurements were performed using the Litesizer 500 (Anton Paar GmbH, Ostfildern, Germany). For each experiment, the average of three results is reported.…”

Section: Methodsmentioning

confidence: 99%

“… 14 , 15 ILs are composed entirely of ions, exist in the liquid state below 100 °C, and are of high chemical tunability. 16 − 18 Uniquely, ILs can be tactically used to enhance the structural and thermal stability of diverse proteins. 14 − 18 While the molecular mechanisms remain largely mysterious, enhanced thermodynamic stability of the native protein state in IL systems has been rationalized in terms of hydrophobic confinement, specific ion effects, and the Hofmeister series.…”

Section: Introductionmentioning

confidence: 99%

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Ionic Liquid-Based Strategy for Predicting Protein Aggregation Propensity and Thermodynamic Stability

Shmool

Martin

Matthews

et al. 2022

JACS Au

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Novel drug candidates are continuously being developed to combat the most life-threatening diseases; however, many promising protein therapeutics are dropped from the pipeline. During biological and industrial processes, protein therapeutics are exposed to various stresses such as fluctuations in temperature, solvent pH, and ionic strength. These can lead to enhanced protein aggregation propensity, one of the greatest challenges in drug development. Recently, ionic liquids (ILs), in particular, biocompatible choline chloride ([Cho]Cl)-based ILs, have been used to hinder stress-induced protein conformational changes. Herein, we develop an IL-based strategy to predict protein aggregation propensity and thermodynamic stability. We examine three key variables influencing protein misfolding: pH, ionic strength, and temperature. Using dynamic light scattering, zeta potential, and variable temperature circular dichroism measurements, we systematically evaluate the structural, thermal, and thermodynamic stability of fresh immunoglobin G4 (IgG4) antibody in water and 10, 30, and 50 wt % [Cho]Cl. Additionally, we conduct molecular dynamics simulations to examine IgG4 aggregation propensity in each system and the relative favorability of different [Cho]Cl-IgG4 packing interactions. We re-evaluate each system following 365 days of storage at 4 °C and demonstrate how to predict the thermodynamic properties and protein aggregation propensity over extended storage, even under stress conditions. We find that increasing [Cho]Cl concentration reduced IgG4 aggregation propensity both fresh and following 365 days of storage and demonstrate the potential of using our predictive IL-based strategy and formulations to radically increase protein stability and storage.

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Section: Discussionmentioning

confidence: 95%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Ionic Liquid-Based Strategy for Predicting Protein Aggregation Propensity and Thermodynamic Stability

Shmool

Martin

Matthews

et al. 2022

JACS Au

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“…On the other hand, the fungicidal action of 10-undecenoic acid has been the subject of research [19][20][21] because it is a very accessible compound [22][23][24] but also because it can be administered in various ways (creams, ointments, sprays or oxide dispersions) [25][26][27].…”

Section: Introductionmentioning

confidence: 99%

Simultaneous Release of Silver Ions and 10–Undecenoic Acid from Silver Iron–Oxide Nanoparticles Impregnated Membranes

et al. 2022

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The bio-medical benefits of silver ions and 10–undecenoic acid in various chemical-pharmaceutical preparations are indisputable, thus justifying numerous research studies on delayed and/or controlled release. This paper presents the effect of the polymer matrix in the simultaneous release of silver ions and 10–undecenoic acid in an aqueous medium of controlled pH and ionic strength. The study took into consideration polymeric matrices consisting of cellulose acetate (CA) and polysulfone (PSf), which were impregnated with oxide nanoparticles containing silver and 10–undecenoic acid. The studied oxide nanoparticles are nanoparticles of iron and silver oxides obtained by an accessible electrochemical method. The obtained results show that silver can be released, simultaneously with 10–undecenoic acid, from an impregnated polymeric membrane, at concentrations that ensure the biocidal and fungicidal capacity. Concentrations of active substances can be controlled by choosing the polymer matrix or, in some cases, by changing the pH of the target medium. In the studied case, higher concentrations of silver ions are released from the polysulfone matrix, while higher concentrations of 10–undecenoic acid are released from the cellulose acetate matrix. The results of the study show that a correlation can be established between the two released target substances, which is dependent on the solubility of the organic compound in the aqueous medium and the interaction of this compound with the silver ions. The ability of 10–undecenoic acid to interact with the silver ion, both through the carboxyl and alkene groups, contributes to the increase in the content of the silver ions transported in the aqueous medium.

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Fundamental advances in hydrogels for the development of the next generation of smart delivery systems as biopharmaceuticals

Nassar

Kasapis

2023

International Journal of Pharmaceutics

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Next generation strategy for tuning the thermoresponsive properties of micellar and hydrogel drug delivery vehicles using ionic liquids

Abstract: Amongst the greatest challenges in developing injectable controlled thermoresponsive micellar and hydrogel drug delivery vehicles include tuning the cloud point (CP) and reducing the gelation temperature (Tgel), below 37 °C,...

Cited by 6 publications

References 57 publications

Ionic Liquid-Based Strategy for Predicting Protein Aggregation Propensity and Thermodynamic Stability

Ionic Liquid-Based Strategy for Predicting Protein Aggregation Propensity and Thermodynamic Stability

Simultaneous Release of Silver Ions and 10–Undecenoic Acid from Silver Iron–Oxide Nanoparticles Impregnated Membranes

Fundamental advances in hydrogels for the development of the next generation of smart delivery systems as biopharmaceuticals

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