title: Sustained Release of Protein Therapeutics from Subcutaneous Thermosensitive Biocompatible and Biodegradable Pentablock Copolymers (PTSgels).
abstract: Objective. To evaluate thermosensitive, biodegradable pentablock copolymers (PTSgel) for sustained release and integrity of a therapeutic protein when injected subcutaneously.Materials and Methods. Five PTSgelswith PEG-PCL-PLA-PCL-PEG block arrangements were synthesized.In vitrorelease of IgG from PTSgelsand concentrations was evaluated at 37°C. Released IgG integrity was characterized by SDS-PAGE.In vitrodisintegration for 10GH PTSgelin PBS was monitored at 37°C over 72 days using gravimetric loss and GPC analysis. Near-infrared IgG in PTSgelwas injected subcutaneously and examined byin vivoimaging and histopathology for up to 42 days.Results. IgG release was modulated from approximately 7 days to more than 63 days in bothin vitroandin vivotesting by varying polymer composition, concentration of PTSgelaqueous solution, and concentration of IgG. Released IgGin vitromaintained structural integrity by SDS-PAGE. Subcutaneous PTSgelswere highly biocompatible andin vitroIgG release occurred in parallel with the disappearance of subcutaneous gelin vivo.Conclusions. Modulation of release of biologics to fit the therapeutic need can be achieved by varying the biocompatible and biodegradable PTSgelcomposition. Release of IgG parallels disappearance of the polymeric gel; hence, little or no PTSgelremains after drug release is complete.
authors: North Carolina State University, Raleigh, NC, USA.
authors: Elizabeth
authors: E
authors: Schaefer
authors: Symmetry Biosciences, Research Triangle Park, NC, USA.
authors: Santhi
authors: 0000-0002-9237-4813
authors: S
authors: Abbaraju
authors: North Carolina State University, Raleigh, NC, USA.
authors: Mary
authors: M
authors: Walsh
authors: North Carolina State University, Raleigh, NC, USA.
authors: Donna
authors: D
authors: Newman
authors: North Carolina State University, Raleigh, NC, USA.
authors: Jacklyn
authors: J
authors: Salmon
authors: Symmetry Biosciences, Research Triangle Park, NC, USA.
authors: Rasidul
authors: R
authors: Amin
authors: i-novion, Inc., Randolph, NJ, USA.
authors: Sidney
authors: S
authors: Weiss
authors: i-novion, Inc., Randolph, NJ, USA.
authors: Ulrich
authors: U
authors: Grau
authors: i-novion, Inc., Randolph, NJ, USA.
authors: Poonam
authors: P
authors: Velagaleti
authors: North Carolina State University, Raleigh, NC, USA.
authors: Brian
authors: 0000-0002-7771-9166
authors: B
authors: Gilger