In Vivo Experimental and Analytical Studies for Bevacizumab Diffusion Coefficient Measurement in the Rabbit Vitreous Humor

Author:

Zhang Shuqi1,Penkova Anita2,Humayun Mark S.3,Martinez-Camarillo Juan Carlos4,Tadle Abegail C.5,Galesic Ana5,Thompson Mark E.6,Pratt Matthew7,Gonzales-Calle Alejandra8,Sadhal Satwindar Singh9

Affiliation:

1. Department of Aerospace & Mechanical Engineering, University of Southern California, USC Viterbi School of Engineering, Los Angeles, CA 90089-1453

2. Department of Aerospace & Mechanical Engineering, University of Southern California, USC Viterbi School of Engineering, Los Angeles, CA 90089-1453; Saban Research Institute, Children's Hospital Los Angeles, Los Angeles, CA 90027

3. Department of Ophthalmology, USC Roski Eye Institute, University of Southern California, Los Angeles, CA 90033-4682; Department of Integrative Anatomical Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033-4682; Department of Biomedical Engineering, University of Southern California, Los Angeles, CA 90089-1111; USC Ginsburg Institute for Biomedical Therapeu

4. Department of Ophthalmology, USC Roski Eye Institute, University of Southern California, Los Angeles, CA 90033-4682; Department of Integrative Anatomical Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033-4682; USC Ginsburg Institute for Biomedical Therapeutics, Department of Ophthalmology, University of Southern California, Los Angeles, CA 90033

5. Department of Chemistry, University of Southern California, Los Angeles, CA 90089-1062

6. Department of Chemistry, University of Southern California, Los Angeles, CA 90089-1062; Mork Family Department of Chemical Engineering & Materials Science, University of Southern California, Los Angeles, CA 90089-1211

7. Department of Chemistry, University of Southern California, Los Angeles, CA 90089-1062; Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089-0371

8. USC Ginsburg Institute for Biomedical Therapeutics, Department of Ophthalmology, University of Southern California, Los Angeles, CA 90033

9. Department of Aerospace & Mechanical Engineering, University of Southern California, USC Viterbi School of Engineering, Los Angeles, CA 90089-1453; Saban Research Institute, Children's Hospital Los Angeles, Los Angeles, CA 90027; Department of Ophthalmology, USC Roski Eye Institute, University of Southern California, Los Angeles, CA 90033-4682; Department of Integrative Anatomical Sciences, Keck

Abstract

Abstract In order to measure the effective diffusion coefficient D of Bevacizumab (Avastin, Genentech) in the vitreous humor, a new technique is developed based on the “contour method” and in vivo optical coherence tomography measurements. After injection of Bevacizumab-fluorescein conjugated compound solution into the rabbit eye, the contours of drug concentration distribution at the subsurface of injection were tracked over time. The 2D contours were extrapolated to 3D contours using reasonable assumptions and a numerically integrated analytical model was developed for the theoretical contours for the irregularly shaped drug distribution in the experimental result. By floating the diffusion coefficient, different theoretical contours were constructed and the least-squares best fit to the experimental contours was performed at each time point to get the best fit solution. The approach generated consistent diffusion coefficient values based on the experiments on four rabbit eyes over a period of 3 h each, which gave D=1.2±0.6×10−6 cm2/s, and the corresponding theoretical contours matched well with the experimental contours. The quantitative measurement of concentration using optical coherence tomography and fluorescein labeling gives a new approach for the “noncontact” in vivo drug distribution measurement within vitreous.

Publisher

ASME International

Subject

Mechanical Engineering,Mechanics of Materials,Condensed Matter Physics,General Materials Science

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