Defense Date

2022

Document Type

Thesis

Degree Name

Doctor of Philosophy

Department

Pharmaceutical Sciences

First Advisor

Qingguo Xu

Abstract

Topical eyedrop is the conventional way for treating front of the eye diseases. However, topical eyedrops have 8 wt% DSP) and sustained drug release for 6 months in rat eyes after a single SCT injection. A single dose of PLA-2COOH8.2kDa DSP-NP not only prevented but also reversed rat corneal graft rejection and maintained the efficacy for 6 months without causing obvious ocular toxicities. Notably, a single dose of PLA-2COOH8.2kDa DSP-NP prevented rat high-risk corneal graft rejection for 6 months. We further developed the combination treatments of PLA-2COOH8.2kDa DSP-NP and sustained delivery of TKI inhibitors through either the axitinib nanowafers or sunitinib malate microparticles for preventing high-risk corneal graft rejection. Both combination treatments prevented grafts rejection for 6 months and demonstrated better treatment efficacy than PLA-2COOH8.2kDa DSP-NP alone.

Studies have shown that Fenofibrate can be a potential drug for diabetic retinopathy (DR) treatment. Intravitreal (IVT) injection is the most commonly used route for drug delivery to the back of the eye, but small molecule drugs like fenofibrate usually get cleared from the eye within several days which limits their clinical use. Here, we developed a fenofibrate loaded PLGA nanoparticles (Feno-NP) with 250nm particle size and >6 wt% drug loading for DR treatment. A single IVT injection of Feno-NP provided 2 months drug release in rat eyes. In vivo efficacy also demonstrated that the single dose of Feno-NP can provide 2 months efficacy for DR treatment. To facilitate the future clinical translation, we developed fenofibrate loaded microparticles (Feno-MP) with >15 wt% drug loading and sustained release for up to 6 months in vitro. We further optimized Feno-MP formulations by applying the SPG membrane emulsification method. Finally, we generated Feno-MPs with uniform size distribution, high drug loading and sustained in vitro drug release for more than 6 months.

Rights

© The Author

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

8-3-2022

Available for download on Monday, August 02, 2027

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