June 2013
Volume 54, Issue 15
Free
ARVO Annual Meeting Abstract  |   June 2013
Evaluating & Predicting Drug Release from an Implantable Biomaterial
Author Affiliations & Notes
  • Ivana Postic
    Chemical Engineering, McMaster University, Hamilton, ON, Canada
  • Heather Sheardown
    Chemical Engineering, McMaster University, Hamilton, ON, Canada
  • Footnotes
    Commercial Relationships Ivana Postic, None; Heather Sheardown, Alcon (F), Alimera Sciences (F)
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2013, Vol.54, 5074. doi:https://doi.org/
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      Ivana Postic, Heather Sheardown; Evaluating & Predicting Drug Release from an Implantable Biomaterial. Invest. Ophthalmol. Vis. Sci. 2013;54(15):5074. doi: https://doi.org/.

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

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Abstract
 
Purpose
 

Drug delivery from siloxane-based materials is attractive due to its inherent properties and biocompatibility. The work describes a siloxane-based matrix with polyethylene glycol (PEG) additive, developed to act as an intra-vitreal implant for release of therapeutics to the posterior segment of the eye. The effects of various constituents on the release rate were examined in order to develop predictable, long-term, controlled drug release.

 
Methods
 

PEG (1-10 wt%, 500-20,000MW) was blended with liquid PDMS (Sylgard® 184 Kit) and 5-10wt% of drug (metformin hydrochloride or ciprofloxacin). Platinum curing agent was added to the entire mixture and cured at 70°C. Quarter-inch discs were punched out and drug release (37°C, 100rpm) into 1ml of posphate buffered saline was measured using UV spectroscopy. ProMV software was used to apply multi-variate methods (ProSensus-Ancaster,Canada). Cytotoxicity testing was performed by incubating PEG/PDMS discs for 48 hours with aRPE19, a retinal pigment epithelium cell line. Cellular metabolism was measured via fluorescence from PrestoBlue reagent.

 
Results
 

Standard analysis showed significant differences in release between the two drug types (Figure 1). Release of hydrophobic ciprofloxacin showed promise for very long-term release (less than 5% released at 17 days). Similar to the release of metformin, the hydrophilicity of the material could be adjusted up to 10wt% and 500MW without significantly affecting the release rate from that of the control. Increasing the concentration of ciprofloxacin from 5wt% to 10wt% allowed for even further prolonged release. Analysis using latent variable methods indicates good fit and predictability of release within the experiments conducted. The drug delivery devices show generally low cytotoxicity when cultured in the presence of aRPE19 cells.

 
Conclusions
 

Release of model drugs metformin and ciprofloxacin shows that this material is suitable for prolonged release of both hydrophobic and hydrophilic molecules. The data provides a basis for predicting polymer & drug formulations that will produce a desired release profile for an intra-vitreal device. The analysis method can be extrapolated to examine and predict release from potentially any biomaterial formulation. Cytotoxicity results support the use of the materials intravitreally.

 
 
Figure 1. Significant difference in release between hydrophobic ciprofloxacin and hydrophilic metformin exists.
 
Figure 1. Significant difference in release between hydrophobic ciprofloxacin and hydrophilic metformin exists.
 
Keywords: 688 retina  
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