PEGylation of paclitaxel for inhaled chemotherapy

Pulmonary 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 th...

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Main Author: Luo, Tian
Format: Thesis (University of Nottingham only)
Language:English
Published: 2016
Subjects:
Online Access:https://eprints.nottingham.ac.uk/35723/
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author Luo, Tian
author_facet Luo, Tian
author_sort Luo, Tian
building Nottingham Research Data Repository
collection Online Access
description Pulmonary 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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format Thesis (University of Nottingham only)
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institution University of Nottingham Malaysia Campus
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language English
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spelling nottingham-357232025-02-28T11:50:20Z https://eprints.nottingham.ac.uk/35723/ PEGylation of paclitaxel for inhaled chemotherapy Luo, Tian Pulmonary 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. 2016-12-14 Thesis (University of Nottingham only) NonPeerReviewed application/pdf en arr https://eprints.nottingham.ac.uk/35723/1/PEGylation%20of%20paclitaxel%20for%20inhaled%20chemotherapy-submitted%20to%20Nottingham.pdf Luo, Tian (2016) PEGylation of paclitaxel for inhaled chemotherapy. PhD thesis, University of Nottingham. Lung cancer; polymer-drug conjugate; PEGylation; pulmonary delivery; paclitaxel
spellingShingle Lung cancer; polymer-drug conjugate; PEGylation; pulmonary delivery; paclitaxel
Luo, Tian
PEGylation of paclitaxel for inhaled chemotherapy
title PEGylation of paclitaxel for inhaled chemotherapy
title_full PEGylation of paclitaxel for inhaled chemotherapy
title_fullStr PEGylation of paclitaxel for inhaled chemotherapy
title_full_unstemmed PEGylation of paclitaxel for inhaled chemotherapy
title_short PEGylation of paclitaxel for inhaled chemotherapy
title_sort pegylation of paclitaxel for inhaled chemotherapy
topic Lung cancer; polymer-drug conjugate; PEGylation; pulmonary delivery; paclitaxel
url https://eprints.nottingham.ac.uk/35723/