Date of Award
1-10-2025
Degree Type
Thesis
Degree Name
Master of Science (MS)
Department
Pharmacology and Experimental Therapeutics
First Advisor
Jawad Fareed
Abstract
Retinoblastoma is the most common intraocular cancer in children, accounting for roughly 9,000 new cases each year—claiming the lives of up to 70% of cases in certain regions of the world. While modern retinoblastoma treatments in developed countries have significantly reduced mortality rates, post-treatment consequences such as vision loss, off-site organ dysfunction, and secondary metastases remain unmet clinical needs. Past studies have confirmed transscleral delivery as an efficacious means to achieve high intraocular drug concentrations possibly superior to the standard systemic regimen of vincristine, etoposide, and carboplatin (VEC) for tumor suppression. This led to several studies exploring the use of biodegradable fibrin sealants as a localized depot delivery to promote drug retention at the scleral surface to forego the complications of systemic injections. To further evaluate this approach, the following research reports on the combinatorial effects of VEC in vitro, the effect of VEC admixture on fibrin sealant kinetics and structure, and the permeability rates of surrogate molecules through porcine scleral tissue in an experimental perfusion model. This research reports VEC as an effective polytherapy in human retinoblastoma cell lines Y79 and WERI inhibition, with Vincristine being a key inclusion for combinatorial efficacy. Structural deviations and coagulation mechanics conclude that fibrin polymerization is impeded by vincristine, but unaffected by incorporation of etoposide or carboplatin. Permeability rates for 6-Carboxyfluorescein and Rhodamine B were established following model validation.
Recommended Citation
Himes, Christopher, "Transcleral Chemotherapeutic Delivery by Fibrin Sealant in the Treatment of Retinoblastoma" (2025). Master's Theses. 4565.
https://ecommons.luc.edu/luc_theses/4565
