June 2020
Volume 61, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2020
Compartmental Model Analysis of Vitreal Drug Concentrations Following Administration of a Sustained Release Drug Delivery System
Author Affiliations & Notes
  • Emily Dosmar
    Biology and Biomedical Engineering, Rose-Hulman Institute of Technology, Terre Haute, Indiana, United States
  • Garet James Bailey
    Biology and Biomedical Engineering, Rose-Hulman Institute of Technology, Terre Haute, Indiana, United States
  • William F Mieler
    Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, Illinois, United States
  • Jennifer J Kang-Mieler
    Biomedical Engineering, Illinois Institute of Technology, Chicago, Illinois, United States
  • Footnotes
    Commercial Relationships   Emily Dosmar, None; Garet Bailey, None; William Mieler, None; Jennifer Kang-Mieler, Illinois Institute of Technology (P)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2020, Vol.61, 2903. doi:
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      Emily Dosmar, Garet James Bailey, William F Mieler, Jennifer J Kang-Mieler; Compartmental Model Analysis of Vitreal Drug Concentrations Following Administration of a Sustained Release Drug Delivery System. Invest. Ophthalmol. Vis. Sci. 2020;61(7):2903.

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

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Abstract

Purpose : The purpose of this study was to examine antibiotic drug transport from a poly(N-isopropylacrylamide)-Polyethylene glycol diacrylate (PNIPAAm-PEG-DA) drug delivery system (DDS) using a computational model. We developed a vancomycin (VAN)-loaded DDS to be delivered via subconjunctival injection. To optimize DDS loading capacity, we used our model to predict the DDS loading dose required to achieve a therapeutic concentration.

Methods : PNIPAAm-PEG-DA hydrogel DDSs loaded with VAN were synthesized and release behavior was characterized in vitro over 504 hours (3 weeks). Based on the Lee and Robinson model of the human eye (2001, 2004, 20042, and 2009) with modification to include sclera, choroid and retina, our model examined VAN diffusion out of the DDS into the subconjunctival space and evaluated the final drug concentration in the vitreous humor. Drug loss to the blood and exchange between each compartment was also considered. Experimental cumulative release data of VAN from DDS was used as the input function. Rate constants were selected based on an extensive literature review and the surface area of all compartments were assumed to be equal (1 cm2). The modeling was simulated using MATLAB software.

Results : The compartment model described was used to simulate the transport of VAN from the DDS contained within the subconjunctival space to the vitreous cavity. Based on the model predictions, it took ~10 hours to achieve 0.007 mg/mL VAN dosing levels in the vitreous. After 24 hours of release, the model predicted the vitreous concentration to be 0.035 mg/mL which is above the peak concentration reported in the aqueous chamber 0.024 mg/mL by Souli et al (2001). Based on our model, our DDS system can achieve a therapeutic level in the vitreous within 10 hours of a single subconjunctival injection and sustain the drug level for a least 24 hours.

Conclusions : The model can be used with various input functions to make clinical predictions without animal subjects. Additionally, our model can be used to explore the minimum loading dose of VAN in our DDS required to achieve a therapeutic drug concentration in the vitreous.

This is a 2020 ARVO Annual Meeting abstract.

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