Synthesis of Polymeric Nanocomposites for Drug Delivery and Bioimaging

Abstract: Nanomaterials have gained great attention for biomedical applications due to their extraordinary physico-chemical and biological properties. The current dissertation presents the design and development of multifunctional nanoparticles for molecular imaging and controlled drug delivery applications which include biodegradable polymeric nanoparticles, superparamagnetic iron oxide nanoparticles (SPION)/polymeric nanocomposite for magnetic resonance imaging (MRI) and drug delivery, manganese-doped zinc sulfide (Mn:ZnS) quantum dots (QDs)/ SPION/ polymeric nanocomposites for fluorescence imaging, MRI and drug delivery.Bioimaging is an important function of multifunctional nanoparticles in this thesis. Imaging probes were made of SPION and Mn:ZnS QDs for in vitro and in vivo imaging. The SPION have been prepared through a high temperature decomposition method to be used as MRI contrast agent. SPION and Mn:ZnS were encapsulated into poly (lactic-co-glycolic) acid (PLGA) nanoparticles during the particles formation. The hydrophobic model drug, busulphan, was loaded in the PLGA vesicles in the composite particles. T2'-weighted MRI of SPION-Mn:ZnS-PLGA phantoms exhibited enhanced negative contrast with r2' relaxivity of 523 mM-1 s-1. SPION-Mn:ZnS-PLGA-NPs have been successfully applied to enhance the contrast of liver in rat model.The biodegradable and biocompatible poly (ethylene glycol)-co-poly (caprolactone) (PEG-PCL) was used as matrix materials for polymeric nanoparticles -based drug delivery system. The PEG-PCL nanoparticles have been constructed to encapsulate SPION and therapeutic agent. The encapsulation efficiency of busulphan was found to be ~ 83 %. PEG-PCL nanoparticles showed a sustained release of the loaded busulphan over a period of 10 h. The SPION-PEG-PCL phantoms showed contrast enhancement in T2'-weighted MRI. Fluorescein-labeled PEG-PCL nanoparticles have been observed in the cytoplasm of the murine macrophage cells (J774A) by fluorescence microscopy. Around 100 % cell viability were noticed for PEG-PCL nanoparticles when incubated with HL60 cell line. The in vivo biodistribution of fluorescent tagged PEG-PCL nanoparticles demonstrated accumulation of PEG-PCL nanoparticles in different tissues including lungs, spleen, liver and kidneys after intravenous administration.