ORCID
https://orcid.org/0009-0002-5075-6167
Date of Award
2023
Document Type
Dissertation
Degree Name
Philosophy (Ph.D)
Department
Pharmaceutical Sciences
First Advisor
Vivek Gupta
Second Advisor
Abu Serajuddin
Third Advisor
Lin Mantell
Abstract
Inhalation route is frequently used to administer drugs for managing respiratory diseases with high pulmonary drug concentration and low systemic side effects. But due to the complex lung structure and defense mechanism, only a small fraction of the dose can reach the lung. There have been several advances in strategies to overcome these challenges and achieve localized delivery to the lung. In this study, we are expanding the scope for lung delivery using a multifunctional delivery system called layer-by-layer (LbL) assembled particles. These are core particles coated with polyelectrolytes multilayer which have a wide range of properties and can be engineered using various core templates and coating polymers. We prepared these particles using polyelectrolyte pair of glycol chitosan and bovine serum albumin coated on polystyrene microspheres. The prepared LbL particles were tested for in-vitro lung deposition which suggests the particles are inhalable and can be explored for therapeutic efficacy in the lung. Next, we loaded Doxorubicin hydrochloride (Dox) into the polyelectrolyte layers of the LbL assembled particles and tested for therapeutic efficacy against small cell lung cancer (SCLC), toxicity in normal lung cells, and cardiomyocytes. The studies confirmed Dox-loaded LbL assembled particles are inhalable with enhanced therapeutic efficacy against SCLC and non-toxic in normal lung cells and cardiomyocytes. We extended the scope of this study by loading a large molecule (GAPDH siRNA) as a component of the polyelectrolyte layers. The prepared particles were tested for in-vitro aerosolization, siRNA integrity, and transfection efficacy in non-small cell lung cancer (NSCLC) cells. The results showed siRNA loaded LbL particles are inhalable with the siRNA secure in the polyelectrolyte layers and provide better transfection efficacy as compared to naked siRNA. This project opens a new chapter into the utility of the LbL assembled particles for efficient delivery of small and large molecules into the lung.
Recommended Citation
Chauhan, Gautam, "LAYER-BY-LAYER ASSEMBLED PARTICLES FOR NON-INVASIVE INHALED THERAPEUTIC DELIVERY TO THE LUNGS" (2023). Theses and Dissertations. 825.
https://scholar.stjohns.edu/theses_dissertations/825