Sustained Release of Protein Therapeutics from Subcutaneous Thermosensitive Biocompatible and Biodegradable Pentablock Copolymers (PTS gels )

Abstract

Objective . To evaluate thermosensitive, biodegradable pentablock copolymers (PTS gel ) for sustained release and integrity of a therapeutic protein when injected subcutaneously. Materials and Methods . Five PTS gels with PEG-PCL-PLA-PCL-PEG block arrangements were synthesized. In vitro release of IgG from PTS gels and concentrations was evaluated at 37°C. Released IgG integrity was characterized by SDS-PAGE. In vitro disintegration for 10GH PTS gel in PBS was monitored at 37°C over 72 days using gravimetric loss and GPC analysis. Near-infrared IgG in PTS gel was injected subcutaneously and examined by in vivo imaging and histopathology for up to 42 days. Results . IgG release was modulated from approximately 7 days to more than 63 days in both in vitro and in vivo testing by varying polymer composition, concentration of PTS gel aqueous solution, and concentration of IgG. Released IgG in vitro maintained structural integrity by SDS-PAGE. Subcutaneous PTS gels were highly biocompatible and in vitro IgG release occurred in parallel with the disappearance of subcutaneous gel in vivo . Conclusions . Modulation of release of biologics to fit the therapeutic need can be achieved by varying the biocompatible and biodegradable PTS gel composition. Release of IgG parallels disappearance of the polymeric gel; hence, little or no PTS gel remains after drug release is complete.