The Efficacy of Polylysine, Lysine Monomer and Polyethylene Glycol as Excipients for the Controlled Release of Nerve Growth Factor from Freeze Dry Silk Scaffolds.
Daruvala, Sanaya T.
- The controlled release of nerve growth factor (NGF) from 2D freeze-dry silk fibroin scaffolds impregnated with various excipients was studied. It is important to develop a suitable release mechanism of NGF from silk scaffolds because it can potentially provide a more effective clinical method for treating conditions such as peripheral nerve injury. This study also advances our knowledge of drug ... read moredelivery in silk scaffolds by quantifying excipient effects on a positively charged protein from the scaffolds. Results may provide guidelines for controlling the release rate of growth factors for other tissue engineering purposes. The porous, NGF-loaded silk scaffolds were prepared with either polylysine, lysine monomer, or polyethylene glycol to see the effect of each on the release mechanism. The excipients were loaded at three different loading levels (0%, 1%, and 10%) and NGF release from the scaffolds was measured over the course of one week. Cumulative release curves were fitted to the power law model to quantify the kinetics of the release and indicate the most relevant release mechanism. The effect of each scaffold type on neuron growth was also studied. SH-SY5Y cells were seeded onto these scaffolds to observe the effect of each excipient on neural growth and differentiation. DRG neuron growth and axon extension was also examined and used as a model for peripheral nerve repair. By observing the effect of these excipients on the cells, we can find a system that approaches a zero-order release mechanism while simultaneously promoting cell growth. Results suggest that polylysine is preferable at low loading levels because it causes the release mechanism to approach zero-order. However, in high doses, we found polylysine to be toxic to both DRGs and SH-SY5Y cells. At higher loading levels, PEG is preferable because it increases the mass NGF released and promotes neurite extension.read less