Microfluidic Production of Alginate Hydrogel Particles for Antibody Encapsulation and Release

Abstract

Owing to their biocompatibility and reduced side effects, natural polymers represent an attractive choice for producing drug delivery systems. Despite few successful examples, however, the production of monodisperse biopolymer-based particles is often hindered by high viscosity of polymer fluids. In this work, we present a microfluidic approach for production of alginate-based particles carrying encapsulated antibodies. We use a triple-flow micro-device to induce hydrogel formation inside droplets before their collection off-chip. The fast mixing and gelation process produced alginate particles with a unique biconcave shape and dimensions of the mammalian cells. We show slow and fast dissolution of particles in different buffers and evaluate antibody release over time.

Cell-laden microfluidic microgels for tissue regeneration

“…For the first case, a classic example would be the crosslinking of alginate with Ca 2+ ions, which attach to the carboxylic acid groups of alginate molecules. 18–20 An example of the latter case would be ionic complementary peptides with alternating positively and negatively charged units that can self-assemble into crosslinked networks. 15 The crosslinking process can be triggered by pH changes, which ionize the functional groups that induce gelation.…”

Versatile, cell and chip friendly method to gel alginate in microfluidic devices

“…Higher viscosity alginate solutions may cause irregular droplet formation. 6 The gelation time was adjusted to avoid clogging of the channels by adjusting the pH to 6.7 in both aqueous solutions, which resulted in no stagnation point gelation at the junction where the aqueous phases meet, and allowed prolonged device operation (more than 12h). The microbeads were produced at a frequency of 282Hz with a mean diameter of 53.2 ± 1.0 µm using flow rates of 50µL/hr and 200 µL/hr for the two alginate solutions and the carrier fluid, respectively.…”

“…Therefore, in addition to having an inlet for Ca 2+ and alginate, an extra inlet is often introduced to the microfluidic geometry whereby sheathing buffer is injected to temporary shield the Ca 2+ stream from the alginate. 6,42,43 The sheathing buffer acts as a barrier to delay diffusion of Ca 2+ ions towards the alginate and therefore slows gelling. Currently, this is the standard approach for alginate fiber synthesis using microfluidic devices, 30,31 but has also been demonstrated for alginate bead synthesis.…”

“…Currently, this is the standard approach for alginate fiber synthesis using microfluidic devices, 30,31 but has also been demonstrated for alginate bead synthesis. 6 The main drawback to this approach is inhomogeneous gelation and complexity in 20 However, the cellviability is strongly dependent on rapidly removing the oleic acid through an on-chip exchange mechanism with mineral oil introduced by an additional channel inlet.…”

Recent trends on hydrogel based drug delivery systems for infectious diseases

“…Thus the NFs hold great potential in the reduction of drug resistance for many infectious diseases. The versatility in the forms of hydrogels that have been manufactured such as particle form (nanogels), 165 inhalable form, 166 liquid injectable form (intravenous and subcutaneous), 167 as a patch for scaffolds 168 and in oral dosages form 169 make them perfect candidate to be exploited for chemotherapy and drug resistance in infectious diseases. For tuberculosis the nanotechnology based systems allows the increased transcytosis in the gut lumen’s M cells which enhance the intracellular uptake in the lining epithelium, and improved uptake in the Peyer’s patch.…”