(332e) Release of Model Macromolecules from Self-Assembling Peptide Hydrogels

Branco, M. C. - Presenter, University of Delaware
Wagner, N. J. - Presenter, University of Delaware
Pochan, D. J. - Presenter, University of Delaware
Schneider, J. P. - Presenter, University of Delaware

Advances in biotechnology techniques have led to the rapid development of small protein and antibody therapeutics. However, several limitations remain in the preparation and delivery of these drugs due to the susceptibility of proteins to degrade during storage and upon administration. To address this problem, hydrogels have been used as delivery devices for these protein drugs. We have designed a class of self-assembling peptides that undergo triggered hydrogelation in response to physiological pH and salt conditions (pH 7.4, 150 mM NaCl). These peptides adopt a random coil conformation in aqueous pH 7.4 solutions and are freely soluble. However, when a physiological relevant concentration of NaCl is added, the peptides fold into a β-hairpin, and subsequently, self-assemble to form a rigid hydrogel stabilized by non-covalent cross-links. For these peptides, it is possible to control the folding and assembly kinetics to form hydrogels with different rigidities. These changes affect the porous morphology within the hydrogel system, and subsequently influence the rate of macromolecular diffusion within the peptide fibrillar network. Another unique characteristic of these hydrogels is that under applied shear, the hydrogel will shear-thin into a low-viscosity gel; however, the gel quickly resets and recovers its initial mechanical rigidity after the applied shear is removed. This property allows hydrogels encapsulating therapeutics to be administered via syringe to target sites for delivery. This study focuses on determining the mass transport properties of model probes from self-assembled MAX8 hydrogels before and after delivery through a syringe. Probes of varying molecular weights and pIs were chosen to assess the effect of fibrillar charge density and hydrogel mesh size on their release properties from these self-assembled networks. Probes are added into solution during folding and self-assembly, yielding gels with macromolecules directly and homogeneously encapsulated into the network.