P.S.R. Naidu1,2, M. Norret2, N.M. Smith2, S.A. Dunlop1, N.L. Taylor2, M. Fitzgerald3, K. Swaminathan, Iyer2*

 

1Experimental and Regenerative Neurosciences, School of Biological Sciences, The University of Western Australia, Perth WA 6009, Australia
2School of Molecular Sciences, The University of Western Australia, Perth WA 6009, Australia
3Curtin Health Innovation Research Institute, Curtin University and the Perron Institute for Neurological and Translational Science, Sarich Neuroscience Research Institute, QEII Medical Centre, Nedlands WA 6009, Australia

 

The use of polymeric nanoparticles for treatment of secondary degeneration that follows neurotrauma may present significant advantages over methods that involve invasive surgical procedures performed on the brain. Nanoparticles may be designed to encapsulate therapeutic agents such that controlled drug delivery can be achieved with minimised systemic sides effects. Additionally, by functionalising the nanoparticles with targeting moieties, the nanoparticles may be able to target the central nervous system and/or breach the blood-brain barrier to provide non-invasive treatment at the site of the injury. A promising treatment currently being investigated pre-clinically involves a novel combination of three calcium channel inhibitors to oligodendrocyte progenitor cells (OPCs) to prevent progressive myelin decompaction that stems from a cascade of destructive biochemical events following neurotrauma.1 We postulate that delivery of this combination of therapeutics as a nanoparticle-based system, may substantially improve the quality of life of neurotrauma patients.

Using spontaneous water-in-oil emulsification, we have successfully synthesised cross-linked poly (hydroxyethyl methacrylate-co-glycidyl methacrylate) (p(HEMA-co-GMA)) nanoparticles that are approximately 260nm in size, as ascertained by Dynamic Light Scattering (DLS) and Transmission Electron Microscopy (TEM). p(HEMA-co-GMA), synthesised via Atom-Transfer Radical Polymerisation (ATRP), has been chosen as the base material for the nanoparticle formulation as the hydrophilic copolymer can allow the entrapment of the promising combination of water-soluble calcium channel inhibitors. NMR and GPC have been used in the characterisation of the copolymer revealing that the copolymer is made up of 20% GMA and 80% HEMA monomers and has a molecular weight of 35kDa and polydispersity index (PDI) of 1.33. Thermogravimetric Analysis (TGA) and Differential Scanning Calorimetry (DSC) confirmed the cross-linked structure within the nanoparticle that can assist in encapsulation and release of the therapeutic agents in a controlled manner. We have been able to functionalise the hydrophilic p(HEMA-co-GMA) nanoparticles with the fluorescent dye, Cy5, to enable diagnostic imaging and tracking. Monoclonal anti-NG2 and TAT peptide were also conjugated on the nanoparticles to allow the targeting of the NG2 proteoglycan on OPCs and to provide the potential to breach the BBB, respectively. Entrapment and controlled release over a period of 7 days of the water-soluble calcium channel inhibitor, oxATP, from within the core of the p(HEMA-co-GMA) nanoparticles was assessed by High Performance Liquid Chromatography (HPLC). With these characteristics, this novel polymeric nanoparticle may be an effective strategy to provide a long-term, non-invasive treatment option using water-soluble therapeutic agents.

 

  1. O'Hare Doig, R. L.; Fitzgerald, M., Novel combinations of ion channel inhibitors for treatment of neurotrauma. Discov Med 2015, 19 (102), 41-7.

 

Biographic Details

Name: Priya S. R. Naidu

Title: PhD Candidate

Affiliation, Country: School of Molecular Sciences, The University of Western Australia

Phone: +618 6488 4474 E-mail: priya.sarapnarajoonaidu@research.uwa.edu.au

Research interests: Polymeric Nanoparticles for Targeted Drug Release

Venue

Room: 
Hawken N201