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Advanced Drug/Gene Delivery systems
Based on our experience in the synthesis of nanoparticles and self-assembled nanoporous layers we develop drug-eluting systems along three main lines: i) drug release from mobile carriers (i.e., drug-conjugated nanoparticles); ii) drug release from fixed devices (i.e., drug-loaded porous coatings on biomedical devices); iii) triggered drug release (with systems that are responsive to magnetic or optical stimuli).

In drug release from mobile carriers we are interested in the design of the carrier itself, which often leads to a hybrid structure (e.g. a magnetic core and a porous shell). The drug can be stored by adsorption or covalent attachment on the surface or inside the pores of the nanoparticles. We also investigate methods to alter the external surface of the nanoparticles (e.g. functionalization with recognition moieties, changing the hydro-phobic or hydrophilic character of the terminal groups, adding spacers to prevent agglomeration and so on).

 

 

From fixed devices: we develop coatings based on mesoporous silica as possible drug eluting reservoirs. The ordered mesoporosity is used to achieve a controlled release of the previously adsorbed drug. Alternatively, the release rate from a membrane-capped reservoir can be controlled by the thickness and porosity of the membrane. Sometimes these devices can be endowed with triggered-release capabilities via inclusion of a suitable receptor (e.g. magnetic or NIR-sensitive nanoparticles). Drug molecules can be integrated within a drug-eluting device (i.e., mixed in the bone cement in orthopedic surgery or in traumatology, adsorbed in internal or external porous structures or loaded in larger internal cavities), or deposited on its external surface. The obvious advantage of using in situ drug eluting devices is that it is possible to deliver therapeutic dosages at target locations while minimizing systemic side effects.

 

Our goal is to control the drug release kinetics from a device either passively (from the intrinsic characteristics of the material) or on demand. In the following images the reader can observe: aluminosilicate crystals coating Titanium supports (left) and MCM-41 microparticles coating PMMA substrates (right).

 

 

 

 

Main collaborations:  
 
  • Dr Nuria Villaboa. La Paz Hospital, Madrid, Spain

     

  • Prof. Carmen Evora, University of La Laguna, Spain.

     

  • Prof. King Yeung, Hong Kong University of Science and Technology, Hong Kong

     

  • Prof. Robert Langer/Daniel Kohane, MIT, USA

     

Some recent related publications:

 
  1. “ Development of magnetic nanostructured silica-based materials as possible vectors for drug-delivery applications” Arruebo, M, et al.Chem. Mater. 18, 1911-19, (2006).  

     

  2.  “Mechanochemical characterisation of silica based-coatings on Nitinol substrates”, Perez, L.M.; Arruebo, M.; et al.  Microp.Mesop. Mater. , 98, 292-302, (2007).  

     

  3.  “Synthesis and characterization of superparamagnetic iron oxide nanoparticles biofunctionalised with a monoclonal antibody anti-hCG”, Arruebo, M., et al., Adv. Funct. Mater. , 17, 1473-79, (2007).  

     

  4. “Magnetic nanoparticles for drug delivery applications” Arruebo, M., et al.  Nano Today, 2, 23-32, (2007).  

     

  5.   “ Synthesis and stealthing study of bare and PEGylated silica micro- and nanoparticles as potential drug delivery vectors” Yagüe, C., et al.  Chem. Eng. J., 137, 42-53, (2008).  

     

  6.  “Preparation of magnetic nanoparticles encapsulated by an ultra-thin silica shell via transformation of Fe-MCM-41”, Arruebo, M., et al.   Chem. Mater., 20, 486-93, (2008).  

     

  7. “Assessing Methods for Blood Cell Cytotoxic Responses to Inorganic Nanoparticles and Nanoparticle Aggregates”, Díaz, B., et al.  Small, 4, 2025-34, (2008).  

     

  8. “Effect of Nitinol surface treatments on its physico-chemical properties” Pérez, L.M., et al.  Journal of Biomedical Materials Research B , 91, 337-47, (2009).  

     

  9. “A magnetically-triggered composite membrane for on-demand drug delivery” Hoare, T., et al.  Nano Lett.,9, 3651-57, (2009).

     

  10.   “Drug delivery from internally implanted biomedical devices used in traumatology and in orthopedic surgery”, Arruebo M., et al., Expert Opinion on Drug Delivery, 7, 589-603, (2010).

     

  11.  "Assessment of the evolution of cancer treatment therapies”. Arruebo et al., Cancers 3, 3279-3330. (2011). 
  12.   Magnetically Triggered Nanocomposite Membranes: A Versatile Platform for Triggered Drug Release. Hoare T. et al., Nano Letters 11, 1395-1400, (2011)

 
 
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