Nanosilicate-hydrogel microspheres formed by aqueous two-phase separation for sustained release of small molecules

Abstract

Introduction: Hydrogel microspheres are an attractive option for drug delivery applications due to their ease of injection and potential for tunable controlled delivery. However, their utility is limited due to high initial burst release and rapid overall release, which is especially pronounced for small molecules or small size microspheres. We and others have shown that the addition of two-dimensional nanosilicate (NS) particles to hydrogels can significantly prolong release kinetics from hydrogels while minimizing burst release.Materials and Methods: Here we explored whether NS could modulate release kinetics of small molecules from small size injectable microspheres. Polyethylene glycol (PEG)-based hydrogel microspheres were fabricated via polymer/salt aqueous two-phase separation (ATPS), which is facile, high yield, and scalable, without the need for organic solvents or oils.Results and Discussion: Importantly, NS and acridine orange (AO), a model cationic small molecule, were shown to phase separate into the PEG-rich phase, allowing for successful encapsulation within hydrogel microspheres. The fabricated microspheres were stable, similar in size to red blood cells, and easily injectable. The effect of various fabrication parameters, including the addition of NS and AO, on microsphere size and polydispersity were explored. Release of AO was significantly slowed from PEG-NS microspheres compared to PEG-only microspheres and correlated with NS concentration. Two additional small molecules, the chemotherapeutic doxorubicin (positive charge), and the model small molecule Brilliant Blue FCF (negative charge), were shown to exhibit prolonged release, underscoring the broad utility of the system. The dependence of release kinetics on encapsulated NS concentration allows for tunable and prolonged release of small molecules from an injectable hydrogel delivery device.

Laponite-Based Nanocomposite Hydrogels for Drug Delivery Applications

“…The use of the Laponite–polymer composite system allows for localized delivery and the opportunity for targeted delivery, which is more difficult to achieve with Laponite particles only. Depending on the geometry and size of the bulk hydrogel, Laponite nanocomposite hydrogels may remain at the desired location longer than when individualized [ 127 ], since Laponite particles may be rapidly cleared due to their small size. For example, Jiang et al developed a hyaluronic acid-based device that allowed for specific targeting of CD44-positive cells, improving the efficacy of doxorubicin delivery [ 123 ].…”

Investigating and Optimizing Insulin Partitioning with Conjugated Au Nanoparticles in Aqueous Two-Phase Systems Using Response Surface Methodology

“…By creating a mechanism that facilitates the transfer of the biomolecule between the two phases, biomolecules partitioning enhances in ATPS. , Nanoparticles fulfill this demand and improve biomolecule partitioning. The high surface-to-volume ratio of nanoparticles makes them attractive carriers, which can greatly enhance extraction performance. , Inorganic nanoparticles, whose structures exhibit significantly different physical, chemical, and biological properties and functionalities compared to their bulk counterparts, have attracted increasing interest. Especially, concerning noble metal nanoparticles, it has been found that their properties are strongly influenced by their shape and size.…”