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Keywords:

  • porous silicon;
  • porous silica;
  • drug delivery;
  • antibody delivery;
  • bevacizumab;
  • sustained drug release

Abstract

Nanostructured mesoporous silica (SiO2) films are used to load and release the monoclonal antibody bevacizumab (Avastin) in vitro. A biocompatible and biodegradable form of mesoporous SiO2 is prepared by electrochemical etching of single crystalline Si, followed by thermal oxidation in air at 800°C. Porous SiO2 exhibits a negative surface charge at physiological pH (7.4), allowing it to spontaneously adsorb the positively charged antibody from an aqueous phosphate buffered saline solution. This electrostatic adsorption allows bevacizumab to be concentrated by >100× (300 mg bevacziumab per gram of porous SiO2 when loaded from a 1 mg mL−1 solution of bevacziumab). Drug loading is monitored by optical interferometric measurements of the thin porous film. A two-component Bruggeman effective medium model is employed to calculate percent porosity and film thickness, and is further used to determine the extent of drug loading into the porous SiO2 film. In vitro drug release profiles are characterized by an enzyme-linked immunosorbent assay (ELISA), which confirms that the antibody is released in its active, VEGF-binding form. The nanostructured delivery system described here provides a sustained release of the monoclonal antibody where approximately 98% of drug is released over a period of one month.