UC San Diego

Recently, attention in chronic inflammation has been increasing since it is closely related to various diseases, such as rheumatoid arthritis, Huntington’s, Parkinson’s, Alzheimer’s diseases, and even in cancers. Inflammation is an immune response against pathogens, damaged cells or irritants. In the process, immune cells activate overproduction of reactive oxygen species (ROS) and decrease pH of the inflammatory area. Therefore, these two biomarkers are available as stimuli for controlled release of drug delivery system (DDS). DDS is intended to encapsulate conventional medicines in vehicles and safely transport the therapeutic agents only to disease area, minimizing adverse effects on normal tissue and maximizing the effect on the target. The ultimate goal of the DDS is to find optimized materials as a delivery vehicle. Polymers are proposed as suitable biomedical materials for several reasons. Firstly, both of hydrophobic conventional drugs and hydrophilic enzymes and proteins can be encapsulated according to polymer nature. Secondly, a wide range of chemical modification is applicable. The easy modification makes efficient delivery possible by controlling the release of cargo by disease-specific stimuli. Based on these advantages, inflammation-responsive polymeric carriers are introduced in here. In chapter 1, ROS-responsive polymeric degradation via chemical amplification is demonstrated. This polymer degraded 12 times faster compared with its control polymer by employing chemical amplification strategy. In chapter 2, anti-inflammatory drug conjugated polymer is introduced. To maximize drug delivery efficiency, an anti-inflammatory drug was conjugated onto dextran using a ROS-responsive linker. This polymeric material not only releases the anti-inflammatory drug in inflammatory cells but also increased drug efficacy by reducing ROS level in inflammation. In chapter 3, bioresponsive prophylaxis polymeric materials for acute inflammation is demonstrated both in vitro and in vivo.