Gel-Mediated Electrospray Assembly of Silica Supraparticles for Sustained Drug Delivery

Supraparticles (SPs) composed of smaller colloidal particles provide a platform for the long-term, controlled release of therapeutics in biomedical applications. However, current synthesis methods used to achieve high drug loading and those involving biocompatible materials are often tedious and low throughput, thereby limiting the translation of SPs to diverse applications. Herein, we present a simple, effective, and automatable alginate-mediated electrospray technique for the assembly of robust spherical silica SPs (Si-SPs) for long-term (>4 months) drug delivery. The Si-SPs are composed of either porous or nonporous primary Si particles within a decomposable alginate matrix. The size and shape of the Si-SPs can be tailored by controlling the concentrations of alginate and silica primary particles used and key electrospraying parameters, such as flow rate, voltage, and collector distance. Furthermore, the performance (including drug loading kinetics, loading capacity, loading efficiency, and drug release) of the Si-SPs can be tuned by changing the porosity of the primary particles and through the retention or removal (via calcination) of the alginate matrix. The structure and morphology of the Si-SPs were characterized by electron microscopy, dynamic light scattering, N2 adsorption–desorption analysis, and X-ray photoelectron spectroscopy. The cytotoxicity and degradability of the Si-SPs were also examined. Drug loading kinetics and loading capacity for six different types of Si-SPs, using a model protein drug (fluorescently labeled lysozyme), demonstrate that Si-SPs prepared from primary silica particles with large pores can load significant amounts of lysozyme (∼10 μg per SP) and exhibit sustained, long-term release of more than 150 days. Our experiments show that Si-SPs can be produced through a gel-mediated electrospray technique that is robust and automatable (important for clinical translation and commercialization) and that they present a promising platform for long-term drug delivery.