Extended Data Fig. 4: In vivo release of bortezomib.
a) Pharmacokinetics of decreasing bortezomib doses administered as subcutaneous boluses without hydrogel. Data is presented as the mean value of four replicates ± SEM. b) The maximum circulating concentration (Cmax) of bortezomib decreases linearly with the initial dose. Dotted lines represent the Cmax for 700 ng of bortezomib delivered from nitroCat-K2 (blue) and SHA-K2 (purple), indicating that a bolus bortezomib dose of 175 ng yields the same Cmax as these hydrogel formulations loaded with 5-fold more drug. c) Chemical structure of the bortezomib fragment observed in mass spectrometry imaging. d) K2, nitroCat-K2, and SHA-K2 hydrogels loaded with 700 ng of bortezomib imaged by mass spectrometry imaging in vitro show very little bortezomib signal, suggesting that MDP peptides suppress the ionization of bortezomib within the gels. This ionization suppression results in dark spots in mass spectrometry images at the location of the hydrogels.
