Non-Viral Gene Delivery from Layer-by-Layer Thin Films

The electrostatic layer-by-layer (LBL) assembly technique is versatile, allowing the incorporation of a broad range of functional polymers and other multiply charged species.The primary aim of this work is to utilize the enabling nanofabrication tool of electrostatic multilayer assembly to create coatings one nanoscale layer at a time by alternating specific drugs with degradable polyions such that complex, multicomponent, sequential or graduated release of drugs takes place from implant surfaces in a layer-by-layer fashion. It is our hypothesis that such hydrolytically degradable nanolayered systems will enable the delivery of precise amounts of drug from a localized area for the remediation of infection and promotion of healing and bone cell growth on joint prosthesis and fracture implants. This method is simple, low cost, and allows the infinite tuning of film composition, and subsequent degradation under biological conditions to release drugs layers at a time.

Significant research has shown the therapeutic impact of growth factor proteins; however a different approach to the introduction of a sensitive biologic protein that has been of recent interest is the introduction of genes that are transfected to cells in or near the bone fracture area, and as a result encode for specific growth proteins. There have been recent publications on the delivery of the BMP gene to bone tissue and cartilage for the promotion of growth and healing of injury and fracture. Some clear advantages of using a gene rather than the original biologic protein in orthopedic applications include the fact that the high concentrations often encountered in administration of proteins by bolus injection or similar means no longer pose a problem with regard to toxicity due to the regulated production provided by cells. Cost is also an important advantage – DNA is generally less expensive than purified growth proteins. DNA is also more stable than most proteins, and has a longer shelf-life. Finally some studies suggest that the proteins generated in vivo from transfected DNA are more active than proteins delivered using other means. Our aim is to determine the feasibility of the delivery of the BMP-2 gene directly from the LBL matrix in place of direct delivery of the actual BMP protein.