Poly(ethylene glycol) Microparticles Produced by Precipitation Polymerization in Aqueous Solution

Abstract

Methods were developed to perform precipitation photopolymerization of PEG-diacrylate. Previously, co-monomers have been added to PEG when precipitation polymerization was desired. In the present method, the LCST of the PEG itself was lowered by addition of the kosmotropic salt sodium sulfate to an aqueous solution. Typical of a precipitation polymerization, small microparticles or microspheres (1–5 micron) resulted with relatively low polydispersity. However, aggregate formation was often severe, presumably due to a lack of stabilization of the phase-separated colloids. Microparticles were also produced by copoymerization of PEG-diacrylate with acrylic acid or aminoethylmethacrylate. The co-monomers affected the zeta potential of the formed microparticles, but not the size. The carboxyl groups of acrylic acid-containing PEG microparticles were activated and scaffolds were formed by mixing with amine-containing PEG microparticles. Although the scaffolds were relatively weak, human hepatoma cells showed excellent viability when present during microparticle crosslinking.

Modular poly(ethylene glycol) scaffolds provide the ability to decouple the effects of stiffness and protein concentration on PC12 cells

“…A sample size of N>1000 microgels was utilized to determine average particle size. The polydispersity of the microgels was calculated as: $$\mathit{PDI}=\frac{\frac{\sum {V_i}^2}{\sum V_i}}{\frac{\sum V_i}{N}}.$$ where V i is the volume of microsphere i and N is the total number of microgels [21]. The size of the microgels was also measured using dynamic light scattering (DLS; 90Plus Particle Size Analyzer, Brookhaven Instruments) at a scattering angle of 90° and wavelength of 658 nm.…”

“…Due to the improved thermal, chemical, and physical properties exhibited by microgels, these particles are currently being investigated for use in a number of applications, including controlled drug delivery [14–17] and tissue engineering applications [18–20]. The preparation of microgels formed via precipitation polymerization creates highly crosslinked microgels with relatively low polydispersity [19, 21] in an aqueous environment. Typically phase separation must be performed at high temperatures, however several groups have demonstrated that the inclusion of kosmotrophic salts allows for precipitation at more physiologically relevant temperatures [21–23].…”

“…The preparation of microgels formed via precipitation polymerization creates highly crosslinked microgels with relatively low polydispersity [19, 21] in an aqueous environment. Typically phase separation must be performed at high temperatures, however several groups have demonstrated that the inclusion of kosmotrophic salts allows for precipitation at more physiologically relevant temperatures [21–23]. To form modugels (scaffolds formed from microgels), active molecules are added during microgel fabrication to influence the degree of crosslinking and overall scaffold stiffness [21, 24].…”

“…Typically phase separation must be performed at high temperatures, however several groups have demonstrated that the inclusion of kosmotrophic salts allows for precipitation at more physiologically relevant temperatures [21–23]. To form modugels (scaffolds formed from microgels), active molecules are added during microgel fabrication to influence the degree of crosslinking and overall scaffold stiffness [21, 24]. The inclusion of extracellular matrix (ECM) components as crosslinkers in forming the modugel then provide the chemical cues necessary for a bioactive scaffold [4].…”

Methods for Generating Hydrogel Particles for Protein Delivery

“…47 Flake et al have also reported precipitation polymerization synthesis of monodisperse PEG microgels between 1 to 5 μm in diameter. 17 …”