October
20,
2016
Dr. Jeoung Soo Lee, Drug Design, Development, and Delivery Laboratory (4D lab), Bioengineering Department, Clemson University (Host: Prof. Glen Kwon)
Neuroplasticity and axonal regeneration in the adult central nervous system are limited by both extrinsic components of the neuronal microenvironment and injury-induced and developmentally-related deficiencies in intrinsic neuronal biochemistry. To overcome these barriers and achieve functional recovery after spinal cord or traumatic brain injury, we have developed a cationic, amphiphilic copolymer (poly(lactide-co-glycolide)-g-polyethylenimine; PgP) as a platform technology for combinatorial delivery of drug and nucleic acid. PgP spontaneously forms polymeric micelle nanoparticles in aqueous solution offering three important capabilities: 1) loading of hydrophobic drugs in the hydrophobic core, 2) electrostatic complexation of nucleic acid therapeutics with the cationic hydrophilic shell, and 3) targeting through surface conjugation of cell-type specific ligands or antibodies. We have shown that PgP is able to efficiently deliver pDNAs and siRNAs to various neural cell types in the presence of serum in vitro, which inhibits the activity of most non-viral vectors. In rat spinal cord compression injury models, local injection of PgP carrying siRNA targeting RhoA reduced cystic cavitation/astrogliosis and stimulated axonal regeneration into the lesion site. In addition, local injection of PgP loaded with the phosphodiesterase inhibitor, rolipram, was able to prevent injury-induced declines in cAMP. Currently, we are evaluating the synergistic effect of combinatorial RhoA siRNA/rolipram delivery on functional recovery, adding neuron-specific targeting and extending their application to traumatic brain injury.
