Date of Award
2022
Document Type
Dissertation
Degree Name
Pharmaceutical Sciences (Ph.D.)
Department
Pharmaceutical Sciences
First Advisor
Vivek Gupta
Second Advisor
Vijaya Korlipara
Third Advisor
Abu Serajuddin
Abstract
Malignant Mesothelioma (MM) is a rare malignancy affecting the mesothelial cells lining major physiological tissues. There is currently no cure for MPM and there is a growing need to bolster the therapeutic arsenal for MPM management. With that in mind, multiple small molecules were screened against MPM models, in-vitro, and it was revealed that Niclosamide (Niclo), an anthelmintic drug, was the most potent against MPM (IC50 values between 1.2-2.2 M) with the ability to inhibit colony formation in MPM cells and is efficacious against 3D tumor models. However, small molecule systemic therapy has resulted in negligible improvement in patient survival relative to a local therapy. So, to develop a localized depot therapy for MPM, a hydrogel-based delivery system is being proposed. Using a design of experiment approach, hydrogel formulation was optimized to yield two formulations with low gelling time, high bio adhesion and a sustained release of small molecules. Further, optimized hydrogels were tested for their potential to carry hydrophilic and hydrophobic therapeutic payloads by loading Doxorubicin hydrochloride (DOX) and Niclo. Developed hydrogels sustained the release of DOX over a period of 12 days, indicating an excellent potential to be a local depot therapy. Therapeutic testing on 2D and 3D MPM tumor models revealed enhanced potency of DOX loaded hydrogels, as compared to plain DOX (p
Recommended Citation
Kulkarni, Nishant S., "RE-INVENTING MALIGNANT PLEURAL MESOTHELIOMA THERAPEUTICS" (2022). Theses and Dissertations. 570.
https://scholar.stjohns.edu/theses_dissertations/570