Johnjoe J Mcfadden

Publications (193) View all

• Source

  Available from: S Ravi P Silva

  Article: Design of double-walled carbon nanotubes for biomedical applications.

  V Neves, E Heister, S Costa, C Tîlmaciu, E Flahaut, B Soula, H M Coley, J McFadden, S R P Silva
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  ABSTRACT: Double-walled carbon nanotubes (DWNTs) prepared by catalytic chemical vapour deposition were functionalized in such a way that they were optimally designed as a nano-vector for the delivery of small interfering RNA (siRNA), which is of great interest for biomedical research and drug development. DWNTs were initially oxidized and coated with a polypeptide (Poly(Lys:Phe)), which was then conjugated to thiol-modified siRNA using a heterobifunctional cross-linker. The obtained oxDWNT-siRNA was characterized by Raman spectroscopy inside and outside a biological environment (mammalian cells). Uptake of the custom-designed nanotubes was not associated with detectable biochemical perturbations in cultured cells, but transfection of cells with DWNTs loaded with siRNA targeting the green fluorescent protein (GFP) gene, serving as a model system, as well as with therapeutic siRNA targeting the survivin gene, led to a significant gene silencing effect, and in the latter case a resulting apoptotic effect in cancer cells.
  Nanotechnology 08/2012; 23(36):365102. · 3.98 Impact Factor
• Article: Behavior of poly(glycerol sebacate) plugs in chronic tympanic membrane perforations.

  C A Sundback, J McFadden, A Hart, K M Kulig, A M Wieland, M J N Pereira, I Pomerantseva, C J Hartnick, P T Masiakos
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  ABSTRACT: The tympanic membrane (TM), separating the external and middle ear, consists of fibrous connective tissue sandwiched between epithelial layers. To treat chronic ear infections, tympanostomy drainage tubes are placed in surgically created holes in TMs which can become chronic perforations upon extrusion. Perforations are repaired using a variety of techniques, but are limited by morbidity, unsatisfactory closure rates, or minimal regeneration of the connective tissue. A more effective, minimally-invasive therapy is necessary to enhance the perforation closure rate. Current research utilizing decellularized or alignate materials moderately enhance closure but the native TM architecture is not restored. Poly(glycerol sebacate) (PGS) is a biocompatible elastomer which supports cell migration and enzymatically degrades in contact with vascularized tissue. PGS spool-shaped plugs were manufactured using a novel process. Using minimally invasive procedures, these elastomeric plugs were inserted into chronic chinchilla TM perforations. As previously reported, effective perforation closure occurred as both flange surfaces were covered by confluent cell layers; >90% of perforations were closed at 6-week postimplantation. This unique in vivo environment has little vascularized tissue. Consequently, PGS degradation was minimal over 16-week implantation, hindering regeneration of the TM fibrous connective tissue. PGS degradation must be enhanced to promote complete TM regeneration. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2012.
  Journal of Biomedical Materials Research Part B Applied Biomaterials 07/2012; 100B(7):1943-54. · 2.15 Impact Factor
• Article: Targeted drug delivery with carbon nanotubes: optimization of drug loading, dispersion stability, and therapeutic efficacy

  E. Heister, V. Neves, C. Lamprecht, S.R.P. Silva, H.M. Coley, J. McFadden
  Carbon 02/2012; 50(2):622 - 632. · 5.38 Impact Factor
• Article: Targeted drug delivery with carbon nanotubes: optimization of drug loading, dispersion stability, and therapeutic efficacy

  E. Heister, V. Neves, C. Lamprecht, S.R.P. Silva, H.M. Coley, J. McFadden
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  ABSTRACT: We have designed a drug delivery system for the anti-cancer drugs doxorubicin and mitoxantrone based on carbon nanotubes, which is stable under biological conditions, allows for sustained release, and promotes selectivity through an active targeting scheme. Carbon nanotubes are particularly promising for this area of application due to their high surface area, allowing for high drug loading, and their unique interaction with cellular membranes. We have taken a systematic approach to PEG conjugation in order to create a formulation of stable and therapeutically effective CNTs. The presented drug delivery system may be a means of improving cancer treatment modalities by reducing drug-related side effects.
  Carbon. 01/2012;
• Article: Uptake and Release of Double-Walled Carbon Nanotubes by Mammalian Cells

  V. Neves, E. Heister, S. Costa, E. Borowiak-Palen, C. Tîlmaciu, E. Flahaut, Coley H. M., Silva, S. R. P., J McFadden
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  ABSTRACT: Efforts to develop carbon nanotubes (CNTs) as nano-vehicles for precise and controlled drug and gene delivery, as well as markers for in vivo biomedical imaging, are currently hampered by uncertainties with regard to their cellular uptake, their fate in the body and their safety. All of these processes are likely to be affected by the purity of CNT preparation, as well as size and concentration of CNT used, parameters often poorly controlled in biological experiments. We demonstrate herein that under the experimental conditions of standard transfection methodologies, DWNTs are taken up by cultured cells but are then released after 24 hours with no discernable stress response. The results support the potential therapeutic use of CNTs in many biomedical settings, such as cancer therapy.
  Advanced Functional Materials 01/2011; 20:3272-3279. · 10.18 Impact Factor