title: Two-layered injectable self-assembling peptide scaffold hydrogels for long-term sustained release of human antibodies.
abstract: The release kinetics for human immunoglobulin (IgG) through the permeable structure of nanofiber scaffold hydrogels consisting of the ac-(RADA)(4)-CONH(2) and ac-(KLDL)(3)-CONH(2) self-assembling peptides were studied during a period of 3 months. Self assembling peptides are a class of stimuli-responsive materials which undergo sol-gel transition in the presence of an electrolyte solution such as biological fluids and salts. IgG diffusivities decreased with increasing hydrogel nanofiber density providing a means to control the release kinetics. Two-layered hydrogel structures were created consisting of concentric spheres of ac-(RADA)(4)-CONH(2) core and ac-(KLDL)(3)-CONH(2) shell and the antibody diffusion profile was determined through the 'onion-like' architecture. Secondary and tertiary structure analyses as well as biological assays using single molecule analyses and quartz crystal microbalance of the released IgG showed that encapsulation and release did not affect the conformation of the antibody and the biological activity even after 3 months inside the hydrogel. The functionality of polyclonal human IgG to the phosphocholine antigen was determined and showed that IgG encapsulation and release did not affect the antibody binding efficacy to the antigen. Our experimental protocol allows for 100% IgG loading efficiency inside the hydrogel while the maximum amount of antibody loading depends solely on the solubility of the antibody in water because the peptide hydrogel consists of water up to 99.5%. Our results show that this fully biocompatible and injectable peptide hydrogel system may be used for controlled release applications as a carrier for therapeutic antibodies.
authors.affiliation: Center for Biomedical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA. sotiris@mit.edu
authors.forename: Sotirios
authors.initials: S
authors.lastname: Koutsopoulos
authors.forename: Shuguang
authors.initials: S
authors.lastname: Zhang
mesh_terms: D000941:Antigens / Q000737:chemistry; D003692:Delayed-Action Preparations; D004337:Drug Carriers / Q000737:chemistry*; D006801:Humans; D020100:Hydrogels / Q000737:chemistry*; D007074:Immunoglobulin G / Q000737:chemistry*; D007267:Injections; D057139:Nanofibers / Q000737:chemistry*; D009842:Oligopeptides / Q000737:chemistry*; D010767:Phosphorylcholine / Q000031:analogs & derivatives / Q000737:chemistry; D012710:Serum Albumin, Bovine / Q000737:chemistry
chemical_list: D000941:Antigens; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D020100:Hydrogels; D007074:Immunoglobulin G; D009842:Oligopeptides; C076110:phosphorylcholine-bovine serum albumin; D010767:Phosphorylcholine; D012710:Serum Albumin, Bovine