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Characterization of Human Sclera Barrier Properties and Development of Episcleral Implant for Transscleral Delivery

Wen, He
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1396454281

Abstract Details

2014, PhD, University of Cincinnati, Pharmacy: Pharmaceutical Sciences/Biopharmaceutics.
Transscleral delivery has been shown to be a promising method to deliver therapeutic agents to the back of the eye for treating ocular diseases. However, the human sclera barrier properties for transscleral permeation are not fully understood. The present dissertation investigated the effects of influencing factors such as the drug lipophilicity, molecular size, and molecular structure on transscleral delivery to characterize human sclera barrier properties. The dissertation also developed an episcleral implant system to provide sustained transscleral delivery of small molecules and a macromolecule. First, the effects of permeant lipophilicity on permeant uptake into and transport across human sclera for transscleral delivery were determined in Chapter 3. Model permeants with a wide range of lipophilicities were studied with human sclera. The partition coefficients, permeability coefficients, and transport lag times of the permeants to human sclera were determined in the uptake and transport experiments. The results showed that permeants with higher lipophilicity exhibited higher partition coefficients and increased apparent transport lag time. No correlation between the permeability coefficient and lipophilicity of the model permeants was observed in this study. In Chapter 4, the scleral partitioning and transscleral permeation of anti-vascular endothelial growth factor (anti-VEGF) drugs bevacizumab and ranibizumab as well as other macromolecular proteins and polysaccharides were investigated. The partition coefficients, permeability coefficients, and transport lag times of the permeants to human sclera were evaluated in the uptake and transport experiments. The macromolecules exhibited low partition coefficients, low permeability coefficients, as well as long transport lag times with human sclera. Macromolecular proteins exhibited lower transscleral permeability coefficients and longer transport lag times than dextrans and ficoll of comparable molecular weights. In Chapter 5, a fiber matrix model was examined for predicting the relationship between transscleral permeability and molecular size of the permeant. The comparison between the values obtained from the fiber matrix model using literature anatomy data of sclera and experimental permeation data in Chapters 3 and 4 showed a deficiency in the fiber matrix model to describe the transport behavior of macromolecules across the sclera. Comparing the predictions from the fiber matrix model and the cylindrical pore model, the fiber matrix model showed a more gradual decrease in the apparent effective diffusion coefficient with the increase of permeant radius. Lastly, a silicone pressure sensitive adhesives (PSA) episcleral implant system was developed and characterized in Chapter 6. Implants for dexamethasone, atenolol, and bovine serum albumin (BSA) were prepared at different polymer-to-drug mass ratios. Drug release experiments were conducted in vitro. The implants had an average diameter of 3.5 mm and thickness of 0.8 mm. The results showed that the implants provided sustained drug release for up to several months in vitro. Drug release from the implants mainly followed a solubility controlled release mechanism with the higher water solubility drug showing higher release rate than the low solubility drug. Increasing polymer content in the implants led to a significant decrease in the drug release rate. Coated implants reduced the initial burst effect and provided lower release rate than the uncoated implants.
Kevin Li, Ph.D. (Committee Chair)
Jinsong Hao, Ph.D. (Committee Member)
Gerald Kasting, Ph.D. (Committee Member)
Chia-Yang Liu, Ph.D. (Committee Member)
R. Randall Wickett, Ph.D. (Committee Member)
186 p.
Pharmaceuticals

Recommended Citations

Citations

  • Wen, H. (2014). Characterization of Human Sclera Barrier Properties and Development of Episcleral Implant for Transscleral Delivery [Doctoral dissertation, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1396454281

    APA Style (7th edition)

  • Wen, He. Characterization of Human Sclera Barrier Properties and Development of Episcleral Implant for Transscleral Delivery. 2014. University of Cincinnati, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1396454281.

    MLA Style (8th edition)

  • Wen, He. "Characterization of Human Sclera Barrier Properties and Development of Episcleral Implant for Transscleral Delivery." Doctoral dissertation, University of Cincinnati, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1396454281

    Chicago Manual of Style (17th edition)

ucin1396454281
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© 2014, all rights reserved.
This open access ETD is published by University of Cincinnati and OhioLINK.