PEGylation of paclitaxel for inhaled chemotherapyTools Luo, Tian (2016) PEGylation of paclitaxel for inhaled chemotherapy. PhD thesis, University of Nottingham.
AbstractPulmonary delivery offers an attractive route for delivering chemotherapeutics, with the benefits of high drug concentrations locally and low side effects systemically. However, fast clearance of small molecules in the lungs and the pulmonary toxicity are the main obstacles in this field. In this thesis, we explored the utility of polyethylene glycol-paclitaxel (PEG-PTX) conjugates to achieve sustained drug release in the lungs. Paclitaxel was linked to 6 kDa and 20 kDa PEG and the conjugates showed good stability and cytotoxicity in vitro. PEG-PTX largely increased the maximum tolerated dose of paclitaxel in mice and significantly enhanced its anti-tumor efficacy following intratracheal instillation in a lung carcinoma mouse model. PEG-PTX 20 kDa presented a prolonged residency and a sustained paclitaxel release in the lungs. This study demonstrated that PEGylation offers a potential delivery system for inhaled chemotherapy with improved anti-tumor efficacy and reduced local toxicity.
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