Complex coacervate core micelles (C3Ms) are nanoscopic structures formed by charge interactions between oppositely charged macroions and used to encapsulate a wide variety of charged (bio)molecules. In most cases, C3Ms are in a dynamic equilibrium with their surroundings. Understanding the dynamics of molecular exchange reactions is essential as this determines the rate at which their cargo is exposed to the environment. Here, we study the molecular exchange in C3Ms by making use of Förster resonance energy transfer (FRET) and derive an analytical model to relate the experimentally observed increase in FRET efficiency to the underlying macromolecular exchange rates. We show that equilibrated C3Ms have a broad distribution of exchange rates. The overall exchange rate can be strongly increased by increasing the salt concentration. In contrast, changing the unlabeled homopolymer length does not affect the exchange of the labeled homopolymers and an increase in the micelle concentration only affects the FRET increase rate at low micelle concentrations. Together, these results suggest that the exchange of these equilibrated C3Ms occurs mainly by expulsion and insertion, where the rate-limiting step is the breaking of ionic bonds to expel the chains from the core. These are important insights to further improve the encapsulation efficiency of C3Ms.
Recent advances in the field of cardiac regeneration show great potential in the use of injectable hydrogels to reduce immediate flush-out of injected factors, thereby increasing the effectiveness of the encapsulated drugs. To establish a relation between cardiac function and retention of the drug-encapsulating hydrogel, a quantitative in vivo imaging method is required. Here, the supramolecular ureido-pyrimidinone modified poly(ethylene glycol) (UPy-PEG) material is developed into a bioactive hydrogel for radioactive imaging in a large animal model. A radioactive label is synthesized, being a ureido-pyrimidinone moiety functionalized with a chelator (UPy-DOTA) complexed with the radioactive isotope indium-111 (UPy-DOTA-111 In) that is mixed with the hydrogel. Additionally, bioactive and adhesive properties of the UPy-PEG hydrogel are increased by supramolecular introduction of a UPy-functionalized recombinant collagen type 1-based material (UPy-PEG-RCPhC1). This method enables in vivo tracking of the nonbioactive and bioactive supramolecular hydrogels and quantification of hydrogel retention in a porcine heart. In a small pilot, cardiac retention values of 8% for UPy-PEG and 16% for UPy-PEG-RCPhC1 hydrogel are observed 4 h postinjection. This work highlights the importance of retention quantification of hydrogels in vivo, where elucidation of hydrogel quantity at the target site is proposed to strongly influence efficacy of the intended therapy.
