Release of peptides from hydrogels 3D-printed by vat photolithography

We report on peptide delivery (absorption and release) from 3D printed hydrogels as a follow up to our previous work [1]. We have examined the influence of tris(2-carboxyethyl) phosphine (TCEP) treatment (a disulphide reducing agent) on the absorption and release characteristics of 3D printed hydrogels for peptide release and delivery illustrating competing pathways of peptide absorption via electrostatic forces and breakage of covalent disulfide linkages derived from residual cysteine residues. We report on two different phosphine reducing agents, TCEP and tris(hydroxypropyl)phosphine (THP) to investigate the effect of carboxylate groups in the phosphine on peptide absorption and subsequent release. The TCEP-treated hydrogels exhibited near complete calcitonin absorption and release, in contrast to low efficiency observed with the THP-treated hydrogels. This discrepancy is attributed to the increased anionic nature of TCEP enabling the formation of electrostatic interactions with the framework of the hydrogel increasing both swelling behaviour and hydrophilicity. This, in turn, enhances the interaction/absorption and release of peptides through electrostatic forces in addition to the covalent disulfide bonds. In contrast, THP-treated hydrogels, which lack these electrostatic interactions, exhibited markedly inferior release rates indicating two separate absorption characteristics namely covalent and electrostatic.