April 2014
Volume 55, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2014
Sustained Release of Bevacizumab (Avastin) from BioSilicon
Author Affiliations & Notes
  • Dinesh Kumar Nadarassan
    Pharmaceutical Sciences, Psivida Corp (pSiMedica), Geraldine Road, United Kingdom
  • Footnotes
    Commercial Relationships Dinesh Nadarassan, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 1950. doi:https://doi.org/
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      Dinesh Kumar Nadarassan; Sustained Release of Bevacizumab (Avastin) from BioSilicon. Invest. Ophthalmol. Vis. Sci. 2014;55(13):1950. doi: https://doi.org/.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: The purpose of this work was to exploit the tunable properties of BioSilicon (a form of oxidized porous silicon) as a substrate to provide long term release Bevacizumab (Avastin). BioSilicon can be manufactured with varying pore size and high surface area. Proteins including antibodies, adsorb by a combination of electrostatic, Van der Waals, and hydrophobic forces, while changes in surface hydration, entropy, and protein structure (shape and size) are also important. Strong electrostatic forces on the surface not only enable the antibody to adsorb but also subsequently desorb from the surface. In this work we evaluated the effect of pore size on Avastin release over a period of three weeks.

Methods: Oxidised porous silicon (OPS) was prepared with pore sizes ranging from of 10 to 100nm (the hydrodynamic radii of Avastin monomer estimated to be ~ 14.52nm). 5mg of OPS was added to 25µL of a 25mg/mL Avastin stock solution (prepared from the commercial formulation) and allowed to equilibrate overnight at room temperature (22.5οC). 1975µL of Phosphate buffer saline (PBS: pH7.4; 37οC) was added to the equilibrated OPS particles. The suspension was then hand mixed for 10 seconds and centrifuged. 1mL of PBS was taken to calculate post loading concentration and 1mL of PBS was freshly added to the dissolution pot. Sampling was performed every 24hrs for 20 days. Samples were analysed by Size-Exclusion Chromatography coupled with UV and fluorescence detectors.

Results: Maximal adsorption was obtained with OPS of average pore size 25 to 30nm which provided approximately 12% (w/w) loading, larger pores gave slightly less loading (10% at 50nm and 8% at 100nm) due to lower surface area. Material with a pore size of 10nm essentially failed to load due to protein size constraints. Release from OPS was highly dependent on pore size with 80% Avastin being released in 20 days from material with pores size of 100nm and less than 10% being released from OPS with a pore size of 25nm.

Conclusions: Long term sustained release of antibodies such as Avastin is achievable by adsorption onto OPS. Release of adsorbed antibody is controllable over a wide range by adjusting the pore size and surface area of OPS. Pore size influences protein adsorption due to size constraints; however, dissolution is also dependent on biodegradation of OPS (wettability of particles).

Keywords: 505 edema • 453 choroid: neovascularization • 659 protein structure/function  
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