title: Remotely triggered scaffolds for controlled release of pharmaceuticals.
abstract: Fe3O4-Au hybrid nanoparticles (HNPs) have shown increasing potential for biomedical applications such as image guided stimuli responsive drug delivery. Incorporation of the unique properties of HNPs into thermally responsive scaffolds holds great potential for future biomedical applications. Here we successfully fabricated smart scaffolds based on thermo-responsive poly(N-isopropylacrylamide) (pNiPAM). Nanoparticles providing localized trigger of heating when irradiated with a short laser burst were found to give rise to remote control of bulk polymer shrinkage. Gold-coated iron oxide nanoparticles were synthesized using wet chemical precipitation methods followed by electrochemical coating. After subsequent functionalization of particles with allyl methyl sulfide, mercaptodecane, cysteamine and poly(ethylene glycol) thiol to enhance stability, detailed biological safety was determined using live/dead staining and cell membrane integrity studies through lactate dehydrogenase (LDH) quantification. The PEG coated HNPs did not show significant cytotoxic effect or adverse cellular response on exposure to 7F2 cells (p < 0.05) and were carried forward for scaffold incorporation. The pNiPAM-HNP composite scaffolds were investigated for their potential as thermally triggered systems using a Q-switched Nd:YAG laser. These studies show that incorporation of HNPs resulted in scaffold deformation after very short irradiation times (seconds) due to internal structural heating. Our data highlights the potential of these hybrid-scaffold constructs for exploitation in drug delivery, using methylene blue as a model drug being released during remote structural change of the scaffold.
authors.affiliation: Guy Hilton Research Centre, Institute of Science and Technology in Medicine, Keele University, Keele, ST4 7QB, UK. c.hoskins@keele.ac.uk.
authors.forename: Paul
authors.initials: P
authors.lastname: Roach
authors.forename: David J
authors.initials: DJ
authors.lastname: McGarvey
authors.forename: Martin R
authors.initials: MR
authors.lastname: Lees
authors.forename: Clare
authors.initials: C
authors.lastname: Hoskins
mesh_terms: D000180:Acrylic Resins; D000818:Animals; D002460:Cell Line; D003692:Delayed-Action Preparations / Q000737:chemistry; D016503:Drug Delivery Systems; D006046:Gold; D006358:Hot Temperature; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D053844:Lasers, Solid-State; D058185:Magnetite Nanoparticles / Q000737:chemistry / Q000648:ultrastructure; D051379:Mice; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D017550:Spectroscopy, Fourier Transform Infrared; D020349:Surface Plasmon Resonance
chemical_list: D000180:Acrylic Resins; D003692:Delayed-Action Preparations; D058185:Magnetite Nanoparticles; C052970:poly-N-isopropylacrylamide; D006046:Gold; D007770:L-Lactate Dehydrogenase