cn400080h_si_001.pdf (397.23 kB)
Assembly of Protein-Based Hollow Spheres Encapsulating a Therapeutic Factor
journal contribution
posted on 2016-02-18, 21:21 authored by Honorata Kraskiewicz, Bridget Breen, Timothy Sargeant, Siobhan McMahon, Abhay PanditNeurotrophins, as important regulators
of neural development, function,
and survival, have a therapeutic potential to repair damaged neurons.
However, a controlled delivery of therapeutic molecules to injured
tissue remains one of the greatest challenges facing the translation
of novel drug therapeutics field. This study presents the development
of an innovative protein–protein delivery technology of nerve
growth factor (NGF) by an electrostatically assembled protein-based
(collagen) reservoir system that can be directly injected into the
injury site and provide long-term release of the therapeutic. A protein-based
biomimetic hollow reservoir system was fabricated using a template
method. The capability of neurotrophins to localize in these reservoir
systems was confirmed by confocal images of fluorescently labeled
collagen and NGF. In addition, high loading efficiency of the reservoir
system was proven using ELISA. By comparing release profile from microspheres
with varying cross-linking, highly cross-linked collagen spheres were
chosen as they have the slowest release rate. Finally, biological
activity of released NGF was assessed using rat pheochromocytoma (PC12)
cell line and primary rat dorsal root ganglion (DRG) cell bioassay
where cell treatment with NGF-loaded reservoirs induced significant
neuronal outgrowth, similar to that seen in NGF treated controls.
Data presented here highlights the potential of a high capacity reservoir-growth
factor technology as a promising therapeutic treatment for neuroregenerative
applications and other neurodegenerative diseases.