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Title

CONTROLLED AND EXTENDED RELEASE OF ANTIANGIOGENIC AGENTS FOR THE ENHANCED TREATMENT OF CHOROIDAL NEOVASCULARIZATION

Creator

Osswald, Christian R.

Date

2015, 2015-07

Description

Current U.S. Food and Drug Administration (FDA)-approved drug therapies for choroidal neovascularization (CNV) secondary to age-related...
Show moreCurrent U.S. Food and Drug Administration (FDA)-approved drug therapies for choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD), also known as wet AMD, require monthly or bimonthly intravitreal (IVT) injections of bolus antiangiogenic agents such as anti-vascular endothelial growth factors (anti-VEGFs) [1]. Less-frequent administration of anti-VEGFs via controlled and extended release is needed to lower the socio-economic impact and lessen the potential side-effects associated with frequent IVT injections. While a controlled delivery system is beneficial, the challenges of initial burst (IB), maintenance of drug bioactivity, and understanding the drug distribution in the diseased eye must be addressed to design an optimal system to address this need. The main goal of this study was to develop a drug delivery system (DDS) capable of delivering anti-VEGF for six months. Additionally, we propose that controlled and extended release of anti-VEGF will yield a greater reduction in CNV growth compared to bolus administration of the same drug. Thus, the current monthly/bimonthly treatment regimen could be replaced by, say, a semi-annual treatment. To accomplish this goal, three specific aims were performed: 1) Development of an injectable microsphere-hydrogel DDS with minimal IB and prolonged release of bioactive anti-VEGF; 2) Verification and validation of the efficacy of said DDS in vivo; and 3) A proof-of-concept finite element analysis comparing the drug distribution throughout a diseased eye to that of a healthy eye.
Ph.D. in Biomedical Engineering, July 2015
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Title

CONTROLLED RELEASE OF VANCOMYCIN FROM A THERMORESPONSIVE HYDROGEL SYSTEM FOR THE PROPHYLACTIC TREATMENT OF POST-OPERATIVE ACUTE ENDOPHTHALMITIS

Creator

Dosmar, Emily

Date

2017, 2017-05

Description

Current clinical treatment for preventing the post-operative endophthalmitis include a bolus injection of the antibiotic, vancoymin (VAN),...
Show moreCurrent clinical treatment for preventing the post-operative endophthalmitis include a bolus injection of the antibiotic, vancoymin (VAN), during surgery followed by a 1-2-week period of patient administered, topically applied antibiotics. Due to poor patient compliance, drug loss due to poor drug residence time for topically applied drops, and limitations of drug injection sites, there is a clinical need for a subconjunctival, sustained release drug delivery system. While a controlled drug delivery system is beneficial by eliminating patient drug administration and improving drug delivery, the challenges of initial burst (IB), drug release kinetics, and drug distribution must be addressed in order to design an optimal system to address this need. The primary goal of this study was to develop a drug delivery system (DDS) capable of delivering VAN for 10-14 days and replacing both the bolus VAN injection and the topical eye drops. We hypothesized that controlled and extended release of VAN will perform equally or better than bolus VAN administration and eye drops. To accomplish this goal, three specific aims were performed: 1) Development of an injectable drug delivery system to release bioactive VAN for at least 10 days; 2) Validation of the efficacy of the developed DDS; and 3) Development of a compartmental model analysis model used to predict the loading dose required to achieve therapeutic drug concentration in the vitreous.
Ph.D. in Biomedical Engineering, May 2017
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