ORCID

https://orcid.org/0009-0009-4699-1915

Date of Award

2026

Document Type

Dissertation

Degree Name

Pharmaceutical Sciences (Ph.D.)

Department

Pharmaceutical Sciences

First Advisor

Vivek Gupta

Second Advisor

Nitesh Kunda

Third Advisor

Ketan Patel

Abstract

Malignant Pleural Mesothelioma (MPM) is a rare yet highly aggressive neoplasm that impacts the mesothelial lining of the lungs. Current therapeutic options primarily consist of various combination therapies, which often come with significant limitations due to their systemic administration. To address these challenges, this study aimed to develop a new formulation for the localized delivery of combination therapy involving small molecules (SJU2, SJU3, and SJU4). In vitro assay revealed that all three compounds exhibited activity against MPM, leading to an analysis of their potential synergistic effects. The synergistic interaction between SJU2 and SJU3 resulted in a reduced dosage requirement, warranting its selection for further investigation. This combination significantly inhibited colony formation (p< 0.005) and cell migration (p< 0.0001) in MPM cells and also demonstrated significant preclinical efficacy in tumor xenograft model. After thorough evaluation of the synergistic effect, a co-loaded formulation was developed. The synergistic drug ratio was preserved throughout the formulation process. This co-loaded formulation significantly enhanced cell death in 3D spheroid of MPM cells (p< 0.0001). Stability studies indicated that the formulation remained stable for two months without significant changes. This study tries to reinvent MPM therapeutics by developing a local non-invasive combination therapy for MPM using an inhaled formulation.

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