) Angiogenic growth factors are essential to tissue growth and repair. Their effective use as therapeutic agents is limited, at least in part, by adequate delivery mechanisms. A novel, water-based delivery system composed of biocompatible and biodegradable polymers can be used to deliver angiogenic growth factors or plasmids encoding these factors in a controlled, sustained, and local fashion. This multicomponent system can be fabricated as nanoparticles or micelles, depending on design needs. Two specific angiogenic factors, basic fibroblast growth factor and vascular endothelial growth factor, will be immobilized individually in polymeric vehicles. Their release kinetics will be adjusted by incorporating additional components such as extracellular matrix to modify their sequestration via electrostatic interactions. Additionally, a physiologic crosslinking agent will be applied post mobilization to create a Schiff base-growth factor adduct. Bioavailability of growth factors will be tested in vitro, and biological efficacy will be tested in vivo in two species. Gene delivery vehicles for plasmid delivery will be formulated as a truncated system, composed of one condensing polymer and a plasm id. Several new polymers, featuring different degrees of hydrophobicity, will be tested towards that; goal using a novel, photon-counting device that detects luciferase reporter expression in vivo. Following, optimization, both of the angiogenic factors and their corresponding expression vectors will be tested in two wound healing models for its ability to induce angiogenesis, as detected by two-dimensional laser doppler imaging and histomorphometry, and wound repair. Extensive biocompatibility testing will be carried out in parallel. A key issue in growth factor and gene therapy is the delivery mechanism. These unique, multicomponent systems can help to circumvent many of the difficulties in clinical application of these angiogenic agents.
| Prokop, Ales; Kozlov, Evgenii; Newman, Gale W et al. (2002) Water-based nanoparticulate polymeric system for protein delivery: permeability control and vaccine application. Biotechnol Bioeng 78:459-66 |
