Local drug delivery systems for enhancement of collateral growth

Abstract

Drug delivery systems are useful tools for local drug delivery in the enhancement of collateral growth (angiogenesis and arteriogenesis). These systems have major clinical potential for patients suffering from coronary artery disease or peripheral artery disease for whom current therapies do not seem to work sufficiently. Administration of drugs for enhancing collateral growth has been used in the past. However, free drug administration may lead to harmful side effects, such as local edema. Therefore, encapsulation of drugs into carriers leads to improved local delivery with its therapeutic effects on collateral growth. Different nano- and microparticles have been developed in the past for drug loading and local drug delivery. These carriers can move through the vasculature without being obstructed. Therefore, they can reach any desired area for stimulation of collateral growth. One type of microparticle is the microbubble (MB), which has been frequently tested in animal models. Different constructs have been developed already for carrying different drug types, such as proteins and gene constructs for cell transfection. Lipid-coated and polymer-coated MBs have been developed in the past. In this thesis, different drug delivery systems will be evaluated for the enhancement of collateral growth. Current therapies tested in experimental studies and clinical trials will be evaluated. The main focus is on new therapeutic approaches for local and sustained drug delivery. Furthermore, suggestions are made for MB constructs to optimize drug delivery for the enhancement of collateral growth.