Hydrophobic payload encapsulation and release characteristics in self-assembled peptide hydrogels
Date
2015
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Publisher
University of Delaware
Abstract
Peptide based hydrogels are an important class of polymeric materials, which have received a large amount of attention for their easy-to-tailor synthesis, biocompatibility, self-assembly into ordered structures and advantageous rheological properties. With twenty-one biologically-relevant amino acids and an ever growing number of synthetic amino acids, countless combinations of potential peptide sequences can be synthesized on the benchtop. The step-by-step synthesis of these peptides leads to precisely controlled amino acid sequences, with predictable physical properties, chemical characteristics and functionalities. In this dissertation, the MAX8 peptide hydrogel is used to encapsulate hydrophobic drugs within a self-assembled, fibrillar network. MAX8 peptide sequences self-assemble at physiological conditions into β-hairpins that form bilayer fibrils with natural branch and entanglement points. In particular, because of this physically crosslinked network, MAX8 is a shear-thinning injectable solid with immediate rehealing behavior. Using rheometry, cytotoxicity assays, spectrophotometry, and liquid scintillation counting, this dissertation examines the successful encapsulation and continuous release of a hydrophobic drug, vincristine, over the course of a month from MAX8 peptide hydrogels. Vincristine, effective at low concentrations, is a commonly used chemotherapeutic that indiscriminately attacks any replicating cell. Despite a month of encapsulation in the aqueous MAX8 hydrogel environment, the vincristine concentrations released are non-zero and retain cytotoxicity. This sustained release of active vincristine, combined with the injectable solid properties of MAX8, demonstrate that MAX8 peptide hydrogels are ideal drug delivery vehicles. Finally, MAX8 hydrogels will have the ability to localize and deliver the potent chemotherapeutic, minimizing unwanted cytotoxicity, while also providing constant treatment. To better characterize the relationship between the hydrophobic vincristine and MAX8 hydrogels, the final chapter of this dissertation utilizes small-angle neutron scattering (SANS) to investigate drug-gel nanostructure. SANS is a powerful technique that characterizes interparticle correlations, which is necessary for understanding the inner hydrogel environment in the presence and constantly changing surrounding concentration of vincristine. The SANS experimental conditions for defining the relationship of a hydrophobic payload in MAX8 hydrogel included time release in different sample environments and the introduction of cisplatin — another hydrophobic chemotherapeutic. Additionally, in this chapter, SANS is employed to quantify the dimensions of a multi-metal/ligand supramolecular gel.