Design and Development of Polymeric Nanoparticles for the Delivery of Therapeutics
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The development of nanoscale drug delivery systems is a rapidly growing field within the realm of nanomedicine, as it has the potential to improve therapeutic efficacy and minimize side effects of various drugs. This dissertation focuses on the rational design, development and application of well-defined polymeric nanoparticles, capable of high loading of both hydrophobic and hydrophilic therapeutic agents, toward the effective treatment of lung diseases. In the first study, cisplatin was loaded into non-degradable poly(acrylic acid)-b-polystyrene-based SCKs through the formation of coordination bonds between platinum and carboxylate groups in the nanoparticle shell domain. The effects of crosslinking were investigated by comparing drug loading & release, in vitro cytotoxicities, and immunotoxicities. In another study, degradable polyphosphoester-based polymeric micelles and SCKs, each derived from non-cytotoxic, amphiphilic block-graft terpolymers, were specifically designed and synthesized for anti-cancer drug paclitaxel (PTX) delivery toward the treatment of osteosarcoma lung metastases. PTX could be encapsulated into either micelles or SCKs, with overall PTX concentration as high as 4.8 mg/mL vs. the low solubility for free PTX in water of less than 2.0 μg/mL. In vivo biodistribution indicated that both micelles & SCKs underwent extravasation from the lung in a controlled manner, while crosslinking slowed the rate of extravasation significantly. Moreover, hydrophilic silver cations were also attached to the nanoparticles via the interaction between silver and alkyne as a potential treatment for bacterial pulmonary infections. The well-defined Ag-loaded nanoparticles released silver in a controlled and sustained manner over 5 days, and displayed enhanced in vitro antibacterial activities against cystic fibrosis-associated pathogens and decreased cytotoxicity to human bronchial epithelial cells, in comparison to silver acetate.
Zhang, Fuwu (2015). Design and Development of Polymeric Nanoparticles for the Delivery of Therapeutics. Doctoral dissertation, Texas A & M University. Available electronically from