Elimination of Unreacted Acrylate Double Bonds in the Polymer Networks of Microparticles Synthesized via Flow Lithography

Abstract

Flow lithography (FL), a versatile technique used to synthesize anisotropic multifunctional microparticles, has attracted substantial interest, given that the resulting particles with complex geometries and multilayered biochemical functionalities can be used in a wide variety of applications. However, after this process, there are double bonds remaining from the cross-linkable groups of monomers. The unreacted cross-linkable groups can affect the particles’ biochemical properties. Here, we verify that the microparticles produced by FL contain a significant number of unreacted acrylate double bonds (UADBs), which could cause irreversible biochemical changes in the particle and pernicious effects to biological systems. We also confirm that the particles contain a considerable number of UADBs, regardless of the various synthetic (lithographic) conditions that can be used in a typical FL process. We present an effective way to eliminate a substantial amount of UADBs after synthesis by linking biochemically inert poly­(ethylene glycol) based on click chemistry. We verify that eliminating UADBs by using this click chemistry approach can efficiently resolve problems, such as the occurrence of random reactions and the cytotoxicity of UADBs.

Direct functionalization of cell‐adhesion promoters to hydrogel microparticles synthesized by stop‐flow lithography

“…To validate that the unreacted acrylate groups of the microparticles are dominant sites for anchoring PLL, we preblocked the remaining acrylate groups with thiolated PEG by thiol‐ene reactions before PLL conjugation and conducted a signal comparison with the intact acrylate groups (Figure 1C). 14 As expected, the fluorescent signals of the blocked microparticles were remarkably lower than those of the unblocked particles, implying that the unreacted acrylate groups were key elements in the conjugation process (Figure 1C).…”

“…To confirm the conjugation of the PLL to particles by a proposed manner, we used PLL labeled with fluorescein isothiocyanate (PLL‐FITC) to qualitatively observe and quantitatively analyze the fluorescent images and signals of attached PLL in the particles. We selected a fluorescent labeling method for the cell‐adhesion promoter since it has powerful advantages for molecular conjugation analysis in hydrogel microparticles, such as the visualization of distributed molecules and the facile quantification of the loaded amount of the molecules by fluorescent intensity 14,21,22,24 …”

“…To synthesize microparticles as a platform for cellular microenvironments, diverse fabrication techniques can be employed, including flow lithography, 7,8 replica molding, 9,10 electrohydrodynamic spraying, 11 and emulsion polymerization based on microfluidics or batch reactors 12,13 . Among these processes, stop‐flow lithography (SFL), one of the representative flow lithographic techniques, is a powerful method for the production of cellular microenvironment structures with tunability on particle size and shape and the production of porous structures for the penetration and diffusion of various biomolecules 8,14 . In particular, the capability of SFL for anisotropic particle synthesis via juxtaposed laminar flow in a microchannel enables cell‐patterning processes in microparticles 2 …”

“…Polyethylene glycol (PEG) is a synthetic polymer, which has been widely and frequently used to produce microparticles by SFL processes as monomers 2,8,14–16 . On the basis of superior biocompatibility and water‐like environment of the PEG hydrogel microparticles, cell‐laden PEG microparticles have been previously synthesized using SFL encapsulating cells suspended in a prepolymer solution in particles during gelation 17 .…”

Design and Use of a Thermogelling Methylcellulose Nanoemulsion to Formulate Nanocrystalline Oral Dosage Forms

“…[31][32][33] These materials are generally not the most ideal excipients for oral drug formulation due to their slow release, [34] large release resistance at high drug loadings, [30,32,33] and potential toxicity. [35] MC is an attractive fasteroding excipient without the above limitations, though formulation approaches have generally not taken advantage of its gelation properties in forming the drug product. To bridge the gap between the use of fast-eroding MC and the efficiency of oral drug formulation, we report a new thermogelling nanoemulsion system.…”