Neural Drug Delivery Systems - First Principles

First Principles

A major challenge of delivering growth factors to lesions in the spinal cord is the high clearance and removal due to the high turnover rate of the cerebrospinal fluid. One way to overcome this is to use a drug delivery system that slowly releases the growth factors over a prolonged period of time. One previously developed affinity-based drug delivery system regulates the slow release of growth factors by binding them to heparin in fibrin gels. In addition to the fibrin gel there are three main components to the heparin-based delivery system (HBDS): a synthetic linker peptide, the polysulfated glycosaminoglycan heparin, and the growth factors being delivered. The synthetic linker peptide is covalently crosslinked to the fibrin gels and is noncovalently linked to heparin, which noncovalently links the desired growth factor to be delivered. The release of the growth factor from heparin is mediated by cell-activated plasmin degradation. When axons extend into the gel, they activate the conversion of plasminogen to plasmin, thereby initiating plasmin degradation of the fibrin gel and release of a growth factor such as NT-3. This drug delivery system has been used extensively to deliver growth factors with a high affinity for heparin, such as basic fibroblast growth factor. It has even been used for some growth factors with lower affinities such as nerve growth factor and NT-3. When HBDS was used to deliver NGF and NT-3, dorsal root ganglion neurite extension was enhanced by 75% and 54% over the controls which included the growth factors freely in media. This drug delivery system presents promisingpotential for in vivo use as an effective way to deliver growth factors to spinal cord lesions and thus promote regeneration.