ORCID

https://orcid.org/0000-0001-7308-6253

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

Lin Mantell

Abstract

Lung cancer remains the leading cause of cancer-related mortality worldwide, with non-small cell lung cancer (NSCLC) accounting for the majority of cases. Although targeted therapies such as the epidermal growth factor receptor tyrosine kinase inhibitor SJU1 have significantly improved clinical outcomes, its therapeutic effectiveness is limited by poor aqueous solubility, off-target systemic exposure, and the development of resistance. Similarly, SJU2, a potent hydrophobic anticancer agent with demonstrated activity against NSCLC, faces substantial challenges related to formulation instability and controlled delivery. These limitations highlight the need for advanced drug-delivery strategies that enable localized combination therapy to enhance anticancer efficacy while minimizing systemic toxicity. The objective of this thesis was to develop an inhalable platform to enable co-delivery of SJU1 and SJU2 for synergistic lung cancer therapy. Poly(lactic-co-glycolic acid) (PLGA) nanoparticles were engineered as a core delivery system and optimized using a quality-by-design (QbD) approach to enhance SJU1 loading and physicochemical stability. Comprehensive physicochemical and release characterization confirmed that the engineered particles were within the respirable range and had enhanced drug release under tumor-relevant conditions. In vitro evaluation in both 2D and 3D cultures demonstrated that SJU1-SJU2 co-delivery resulted in significantly enhanced cytotoxicity and synergistic anticancer activity compared to single-drug treatments. Overall, this work establishes a versatile inhalable nanoparticle platform that overcomes solubility and delivery challenges of hydrophobic anticancer agents and enables effective localized combination therapy for lung cancer.

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