Active droplets in a hydrogel release drugs with a constant and tunable rate

Wanzke, Caren; Tena‐Solsona, Marta; Rieß, Benedikt; Tebcharani, Laura; Boekhoven, Job

doi:10.1039/c9mh01822k

Cited by 40 publications

(54 citation statements)

References 43 publications

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“…All emulsions in this work follow the same experimental design (Figure 1), i. e ., a water‐soluble precursor (A) molecule is activated by an irreversible reaction with a fuel [38,39] . The product of that reaction (B) is less soluble and phase‐separates into droplets.…”

Section: Resultsmentioning

confidence: 99%

Accelerated Ripening in Chemically Fueled Emulsions**

et al. 2020

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Chemically fueled emulsions are solutions with droplets made of phase‐separated molecules that are activated and deactivated by a chemical reaction cycle. These emulsions play a crucial role in biology as a class of membrane‐less organelles. Moreover, theoretical studies show that droplets in these emulsions can evolve to the same size or spontaneously self‐divide when fuel is abundant. All of these exciting properties, i. e., emergence, decay, collective behavior, and self‐division, are pivotal to the functioning of life. However, these theoretical predictions lack experimental systems to test them quantitively. Here, we describe the synthesis of synthetic emulsions formed by a fuel‐driven chemical cycle, and we find a surprising new behavior, i. e., the dynamics of droplet growth is regulated by the kinetics of the fuel‐driven reaction cycle. Consequently, the average volume of these droplets grows orders of magnitude faster compared to Ostwald ripening. Combining experiments and theory, we elucidate the underlying mechanism.

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Section: Resultsmentioning

confidence: 99%

Accelerated Ripening in Chemically Fueled Emulsions**

et al. 2020

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“…1), i.e., a water-soluble precursor (A) molecule is activated by an irreversible reaction with a fuel. 28,29 The product of that reaction (B) is less soluble and phase-separates into droplets. Moreover, this product B is intrinsically unstable and spontaneously deactivates via hydrolysis, yielding the original precursor A.…”

Section: Resultsmentioning

confidence: 99%

“…The linear decay is a result of the constant deactivation rate (hydrolysis), which is induced by a self-protection mechanism of the droplets. 27,29 Because the droplets do not contain water, the deactivation can take place at the interface of a droplet and on the product fraction that remains in the aqueous phase (i.e., outside of the droplets), which is close to the solubility (! out (#) ).…”

Section: Fig 2 Chemical Reaction Cycles Yielding Emulsions A) Fourmentioning

confidence: 99%

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Kinetic Control over Droplet Ripening in Fuel-Driven Active Emulsions

Tena‐Solsona¹,

Janssen²,

Wanzke³

et al. 2020

Preprint

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Active droplets are made of phase-separated molecules that are activated and deactivated by a metabolic reaction cycle. Such droplets play a crucial role in biology as a class of membrane-less organelles. Moreover, theoretical studies show that active droplets can evolve to the same size or spontaneously self-divide when energy is abundant. All of these exciting properties, i.e., emergence, decay, collective behavior, and self-division, are pivotal to the functioning of life. However, these theoretical predictions lack experimental systems to test them quantitively. Here, we describe the synthesis of synthetic active droplets driven by a metabolic chemical cycle and we find a surprising new behavior, i.e., the dynamics of droplet-growth is regulated by the kinetics of the fuel-driven reaction cycle. Consequently, these droplets ripen orders of magnitude faster compared to Ostwald ripening. Combining experiments and theory, we elucidate the underlying mechanism, which could help better understand how cells regulate the growth of membrane-less organelles.<br>

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“…It is likely that the increased steric bulk of both surfactant and the thiol, combined with the lower solubility of the thiol results in a slow catabolic process. [29] To create an out-of-equilibrium system, continuous formation and destruction of 7 are required here. We envisioned that the breakdown of 7 could be promoted by a nucleophilic catalyst, [30] thereby creating a second, coupled metabolic cycle (Figure 4 a).…”

Section: Angewandte Chemiementioning

confidence: 99%

Coupled Metabolic Cycles Allow Out‐of‐Equilibrium Autopoietic Vesicle Replication

et al. 2020

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We report chemically fuelled out-of-equilibrium selfreplicating vesicles based on surfactant formation. We studied the vesicles autocatalytic formation using UPLC to determine monomer concentration and interferometric scattering microscopy at the nanoparticle level. Unlike related reports of chemically fuelled self-replicating micelles, our vesicular system was too stable to surfactant degradation to be maintained out of equilibrium. The introduction of a catalyst, which introduces a second catalytic cycle into the metabolic network, was used to close the first cycle. This shows how coupled catalytic cycles can create a metabolic network that allows the creation and perseverance of fuel-driven, out-of-equilibrium self-replicating vesicles. One of the great challenges in chemistry is to mimic the complex living structures found in nature by designing artificial out-of-equilibrium systems. [1] These structures involve functional, dynamic states which require a continuous supply of energy to be sustained. [2] This energy can be supplied as a chemical fuel, or another energy source such as light. [3] Systems that use an energy supply to maintain behaviour that would otherwise not persist, are known as dissipative systems. [4] Upon depletion or removal of the energy source, the rates of destruction and formation become unbalanced and the system moves to thermodynamic equilibrium. By maintaining complex systems in an out-ofequilibrium state different behaviour can be observed compared to systems in equilibrium. This includes novel selfassembly processes, [5] material properties [6] and functionality. [7] Out-of-equilibrium systems are frequently encountered in phase-separated systems, where functionalities such as product selection [8] or self-regulation [9] can be observed. Especially interesting is the creation of synthetic supramolecular vesicles, since these resemble cellular structures found in nature. [10] Both functional transient vesicles, [11] and thermo-[*] Dr. A

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Active droplets in a hydrogel release drugs with a constant and tunable rate

Abstract: Materials that release drugs with a constant, zero-order rate are of great importance to improve therapeutic efficacy and reduce toxic side effects.

Cited by 40 publications

References 43 publications

Accelerated Ripening in Chemically Fueled Emulsions**

Accelerated Ripening in Chemically Fueled Emulsions**

Kinetic Control over Droplet Ripening in Fuel-Driven Active Emulsions

Coupled Metabolic Cycles Allow Out‐of‐Equilibrium Autopoietic Vesicle Replication

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