Microfluidic encapsulation of nanoparticles in alginate microgels gelled via competitive ligand exchange crosslinking

Abstract

Efficient delivery of nanometric vectors complexed with nanoparticles at a target tissue without spreading to other tissues is one of the main challenges in gene therapy. One means to overcome this problem is to confine such vectors within microgels that can be placed in a target tissue to be released slowly and locally. Herein, a conventional optical microscope coupled to a common smartphone was employed to monitor the microfluidic production of monodisperse alginate microgels containing nanoparticles as a model for the encapsulation of vectors. Alginate microgels (1.2%) exhibited an average diameter of 125 ± 3 μm, which decreased to 106 ± 5 μm after encapsulating 30 nm fluorescent nanoparticles. The encapsulation efficiency was 70.9 ± 18.9%. In a 0.1 M NaCl solution, 55 ± 5% and 92 ± 4.7% of nanoparticles were released in 30 minutes and 48 hours, respectively. Microgel topography assessment by atomic force microscopy revealed that incorporation of nanoparticles into the alginate matrix changes the scaffold's interfacial morphology and induces crystallization with the appearance of oriented domains. The high encapsulation rate of nanoparticles, alongside their continuous release of nanoparticles over time, makes these microgels and the production unit a valuable system for vector encapsulation for gene therapy research.

Advanced Microfluidic Technologies for Lipid Nano-Microsystems from Synthesis to Biological Application

“…Recently, droplet-based microfluidics has been explored to form hydrogels in discrete volumes with characteristic dimensions in the range of micrometers and polydispersity values up to 2% [173,174]. From this perspective, microfluidics has been used to encapsulate within microgels small drugs [175], proteins [176,177], nanoparticles [81,178], liposomes [179][180][181][182], viral-vectors [183,184], and non-viral vectors [177]. In drug delivery, droplet-microfluidics have been investigated to associate liposomes and polymeric matrices to form liposomes-in-microgels [179][180][181][182]185] and lipobeads [186].…”

Trends in hydrogel-based encapsulation technologies for advanced cell therapies applied to limb ischemia

“…Thus, the characteristics of formed structures can be precisely changed by modulating fluid properties, microchannel design, and parameter processes, such as the flow rate of fluids. In addition, since low shear stress is applied, many sensitive biological materials, such as proteins, vectors, and cells, can be encapsulated without incurring significant damage [ [49] , [50] , [51] , [52] ].…”