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

• Peptide Delivery Efficiency : • Peptide absorption and release from 3D-printed hydrogels, with particular attention to the impact of disulfide reduction agents on peptide delivery. • Role of phosphine based reducing agents :Tris(2-carboxyethyl) phosphine (TCEP) enhances calcitonin absorption and release by increasing the hydrogel’s anionic nature, which fosters electrostatic interactions and swelling behavior, improving peptide delivery efficiency. • Comparison with THP with TCEP :Hydrogels treated with tris(hydroxypropyl)phosphine (THP), which lacks carboxylate groups, show significantly lower absorption and release rates, highlighting the importance of electrostatic interactions in peptide delivery. • 3D Printing Applications :Advances in 3D printing, especially digital light processing (DLP), enable high-resolution fabrication of hydrogels and other biocompatible structures for drug delivery and tissue engineering. • Challenges in Drug Delivery : • Despite progress in 3D-printed drug delivery systems, challenges like premature drug release and environmental influence on release rates remain, necessitating further refinement we offer a potential solution. • Disulfide Bond Mechanism : • Use of disulfide bonds in hydrogels to facilitate reversible chemical interactions for peptide absorption and release, offering selective and controlled delivery, particularly in reductive environments. 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.