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Near-infrared light-activated polymeric micro and nanoparticle systems for controlled and targeted drug delivery: a dissertation in Biomedical Engineering and Biotechnology
Dissertation   Open access

Near-infrared light-activated polymeric micro and nanoparticle systems for controlled and targeted drug delivery: a dissertation in Biomedical Engineering and Biotechnology

Mishal Pokharel
Doctor of Philosophy (PHD), University of Massachusetts Dartmouth
2025
DOI:
https://doi.org/10.62791/20527

Abstract

The pursuit of advanced drug delivery systems emphasizes the need for precision, site-specificity, and temporal control. This thesis presents a multi-faceted approach to the design and development of light-responsive micro/nanoparticle-based systems, integrating biomaterials science, fabrication techniques, and optical manipulation tools for targeted and controlled drug release. Leveraging the biocompatibility and versatility of poly (lactic-co-glycolic acid) (PLGA) and ethyl cellulose(EC), various particles were fabricated using emulsion-based, solvent displacement method, and quasi-emulsion solvent diffusion methods to encapsulate therapeutic agents such as salicylic acid, dacarbazine (DTIC), vancomycin hydrochloride, cisplatin, and cranberry extract. A key innovation in this work lies in the incorporation of near-infrared (NIR) responsive materials, including indocyanine green (ICG) and silver nanoparticles (AgNPs), into the carriers for externally triggered, on-demand drug release. These systems demonstrated high encapsulation efficiencies and sustained drug release profiles, with chitosan-coated PLGA particles effectively suppressing premature drug leakage in the absence of NIR light. NIR-triggered exposure enhanced therapeutic outcomes, reducing bacterial colony formation in vancomycin-loaded microparticles and inducing cytotoxic effects in melanoma A375 cells in DTIC and Cisplatin-loaded nanoparticles. Cytotoxicity and drug release assays confirmed the controlled, minimally harmful nature of the system under non-stimulated conditions. Additionally, this research explores the fabrication of Genipin crosslinked PVA-Chitosan hydrogels and micro-needle patches for controlled release of the micro/nanocarriers for the treatment of skin melanoma. Collectively, this research highlights the synergy between responsive biomaterials, fabrication methods, and photonic control systems in creating next-generation drug delivery platforms. These systems hold promises for translational applications in inflammation treatment, infectious disease management, and targeted cancer therapy, laying the groundwork for precise, adaptable, and effective therapeutic interventions.
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