Diverse Strategies to Develop Poly(ethylene glycol)-Polyester Thermogels for Modulating the Release of Antibodies.

In this work, we present basic research on developing thermogel carriers containing high amounts of model antibody immunoglobulin G (IgG) with potential use as injectable molecules. The quantities of IgG loaded into the gel were varied to evaluate the possibility of tuning the dose release. The gel materials were based on blends of thermoresponsive and degradable ABA-type block copolymers composed of poly(lactide-co-glycolide)-b-poly(ethylene glycol)-b-poly(lactide-co-glycolide) (PLGA-PEG-PLGA) or poly(lactide-co-caprolactone)-b-poly(ethylene glycol)-b-(lactide-co-caprolactone) (PLCL-PEG-PLCL). Primarily, the gels with various amounts of IgG were obtained via thermogelation, where the only factor inducing gel formation was the change in temperature. Next, to control the gels' mechanical properties, degradation rate, and the extent of antibody release, we have tested two approaches. The first one involved the synergistic physical and chemical crosslinking of the copolymers. To achieve this, the hydroxyl groups located at the ends of the PLGA-PEG-PLGA chain were modified into acrylate groups. In this case, the thermogelation was accompanied by chemical crosslinking through the Michael addition reaction. Such an approach increased the dynamic mechanical properties of the gels and simultaneously prolonged their decomposition time. An alternative solution was to suspend crosslinked PEG-polyester nanoparticles loaded with IgG in a PLGA-PEG-PLGA gelling copolymer. We observed that loading IgG into thermogels lowered the gelation temperature (T