Ultrasound-Triggered Delivery of Iproplatin from Microbubble-Conjugated Liposomes |
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| Authors: | Dr Richard Browning Nia Thomas Laura K Marsh Dr Louise R Tear Dr Joshua Owen Prof Dr Eleanor Stride Dr Nicola J Farrer |
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| Institution: | 1. Institute of Biomedical Engineering, University of Oxford, Oxford, OX3 7DQ UK;2. Chemistry Research Laboratory, University of Oxford, 12 Mansfield Road, Oxford, OX1 3TA UK |
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| Abstract: | The PtIV prodrug iproplatin has been actively loaded into liposomes using a calcium acetate gradient, achieving a 3-fold enhancement in drug concentration compared to passive loading strategies. A strain-promoted cycloaddition reaction (azide- dibenzocyclooctyne) was used to attach iproplatin-loaded liposomes L(Pt) to gas-filled microbubbles (M), forming an ultrasound-responsive drug delivery vehicle M−L(Pt)]. Ultrasound-triggered release of iproplatin from the microbubble-liposome construct was evaluated in cellulo. Breast cancer (MCF-7) cells treated with both free iproplatin and iproplatin-loaded liposome−microbubbles M−L(Pt)] demonstrated an increase in platinum concentration when exposed to ultrasound. No appreciable platinum uptake was observed in MCF-7 cells following treatment with L(Pt) only or L(Pt)+ultrasound, suggesting that microbubble-mediated ultrasonic release of platinum-based drugs from liposomal carriers enables greater control over drug delivery. |
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| Keywords: | cancer drug delivery iproplatin liposome ultrasound |
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