Investigation of Vape Devices as Novel Drug Delivery Systems Using Fluorine-18 Radiolabelling

JOURNAL OF NUCLEAR MEDICINE(2021)

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1464 Introduction: Compared to the conventional oral and intravenous routes, pulmonary drug delivery offers superior drug concentrations in the lung for rapid efficacy and improved patient compliance. Vapes represent an under explored alternative drug delivery system which could address the performance limitations of other devices. The development and validation of effective inhaled medications is often challenging. Positron emission tomography (PET) has been previously employed to validate novel drug delivery systems.1 PET can be used in pre-clinical proof-of-concept in vitro/ vivo studies focussing on pulmonary penetration, deposition and clearance. Results from these studies can be used to optimize performance for clinical trials by making informed changes to the device or formulation.\n Methods: Variable temperature control vapes were employed with rebuildable atomisers to allow for control over device properties. A bespoke automated rig was fabricated for the vape to ensure reproducibility. Performance was quantified using an imaging probe (18F-V1) that was designed and synthesised to ensure appropriate miscibility, volatility and stability. The molecule was also assessed in a jet nebulizer to provide direct comparison. Flow rate, percentage of glycerol, vape duration, coil temperature and coil resistance were all varied to determine optimal parameters. Preliminary output and stability studies were performed using radiolabelled drug molecules (18F-fluticasone propionate2 (18F-FP) and 18F-fleroxacin3 (18F-FLX)).\n Results: 18F-V1 was radiolabelled using a K222/K18F complex and isolated by distillation in good yield (decay corrected RCY 46.2 ± 15.8 %, n = 13, RCP \u003e 98%). The vape liquid was prepared comprising vegetable glycerol, propylene glycol and 18F-V1 for addition to the device. 18F-V1 was shown to be stable by HPLC after vaping at 315°C. Glycerol percentage and flow rate appeared to have little effect on device output whereas varying the coil resistance and vape duration had significant effect and coil temperate drastically altered output. Compared to jet nebulisers, vapes show a vastly improved output (13.5% vs 0.18% activity output per second). Initial studies with 18F-FLX indicated decomposition (~60%) at higher coil temperatures (315°C) but the tracer was stable at lower temperature (100°C), although the output was greatly reduced (0.29% per second). 18F-FP remained stable at high temperature (315°C) and demonstrated promising output statistics from a short 4s vape (4.08% per second).\n Conclusions: A novel molecular probe was successfully synthesized and radiolabelled, allowing for the successful quantification of vape device output. Device parameters were varied to understand their influence on device performance. Initial drug output studies show promising results and warrant further investigation.\nAcknowledgements: The authors would like to thank the UoH for a scholarship to GH, Drug Delivery to the Lungs Society for funding from the Career Development Grant, the Daisy Appeal and Dr Assem Allam and family for their generous contribution to the University of Hull PET Research Centre.\nReferences: 1. Cossi U., et al, Preclinical evaluation of aerosol administration systems using Positron Emission Tomography, Eur. J. Pharm. Biopharm., 2018. 130: p. 59-65.2. Neal T., et al., Improved synthesis of [18F]fluoromethyl tosylate , a convenient reagant for radiofluoromethylations, J. Label. Compd. Radiopharm., 2005. 48: p. 557-68.3. Livni E., et al., Synthesis and biodistribution of 18F-labelled Fleroxacin, Nucl. Med. Biol., 1993. 20 (1): p. 81-7.
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vape devices,novel drug delivery systems,drug delivery
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