Factors affecting size and swelling of poly(ethylene glycol) microspheres formed in aqueous sodium sulfate solutions without surfactants

Abstract

The LCST behavior of poly(ethylene glycol) (PEG) in aqueous sodium sulfate solutions was exploited to fabricate microspheres without the use of other monomers, polymers, surfactants or organic solvents. Reactive PEG derivatives underwent thermally induced phase separation to produce spherical PEG-rich domains that coarsened in size pending gelation, resulting in stable hydrogel microspheres between ≈1–100 microns in size. The time required to reach the gel point during the coarsening process and the extent of crosslinking after gelation both affected the final microsphere size and swelling ratio. The gel point could be varied by pre-reaction of the PEG derivatives below the cloud point, or by controlling pH and temperature above the cloud point. Pre-reaction brought the PEG derivatives closer to the gel point prior to phase separation, while the pH and temperature influenced the rate of reaction. Dynamic light scattering indicated a percolation-to-cluster transition about 3–5 minutes following phase separation. The mean radius of PEG-rich droplets subsequently increased with time to the 1/4th power until gelation. PEG microspheres produced by these methods with controlled sizes and densities may be useful for the production of modular scaffolds for tissue engineering.

Alginate microsphere filled with carbon nanotube as drug carrier

“…For example, the loaded drugs can be released together with the swelling of microsphere under the given pH while the swelling behavior can also be used to regulate the period of drug release. Herein, the composition [24], cross-linking density [25] and porous structure [26] become the main factors to affect the swelling process of microsphere and the diffusion of encapsulated substances, especially for the therapeutic macromolecules of protein [27] and peptide [28] as well as cells [29]. Currently, the pH sensitivity of AL-based microspheres has been used to elevate the stability of drug [30], to improve gastrointestinal tolerance [31], to realize sustained release after oral administration [32], and to targetedly release drug in intestine and colon [33].…”

The formation of protein concentration gradients mediated by density differences of poly(ethylene glycol) microspheres

“…Evidently, some microspheres were adhering to the glass walls and not migrating properly. The presence of amines in the microspheres makes them net cationic, [29] probably promoting adhesion to the anionic silanol groups on the glass. The glass was thus coated with PLL- g -PEG to prevent the microspheres from adhering to the glass walls.…”

“…The maximum number of clearly defined tiers of microspheres that we were able to form was three (Figure 5). We previously showed a nonlinear relationship between density, and incubation time, with large changes in swelling (and presumably density) soon after microspheres begin to form, but with a long plateau with a slow rate of change in swelling at longer incubation times [29]. Incubation times resulting in well defined 3-tier gradient were 11, 17, and 45 minutes.…”

“…The relationship between crosslink density and swelling is described by the well-known Flory-Rehner equation [39]. However, we previously found that the decrease in swelling with increasing crosslinking time was not readily described in the Flory-Rehner framework other than qualitatively [29]. Intuitively, one would expect that soon after gelation, the number of crosslinks should increase rapidly.…”

“…We have found that varying the temperature of the phase separation and the amount of time the PEG is allowed to react above the cloud point allows us to control both the size and the density (buoyancy) of the microspheres. The size of microspheres in their de-swollen state is controlled primarily by the time to reach the gel point, while the swelling following buffer exchange into PBS is determined by crosslink density [29]. The swelling of the microsphere should greatly affect the density of the microspheres by changing the ratio of solvent to polymer.…”