99m-Technetium as a marker of liposomal deposition and clearance in the human lung |
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Authors: | S.J. Farr I.W. Kellaway D.R. Parry-Jones S.G. Woolfrey |
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Affiliation: | 1. Welsh School of Pharmacy, UWIST, Cardiff CF1 3XF, U.K.;2. Department of Medical Physics, University Hospital of Wales, Heath Park, Cardiff CF4 4XN, U.K. |
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Abstract: | The clearance of pulmonary delivered 99mTc-labelled dipalmitoyl phosphatidylcholine (DPPC) liposomes has been studied in 4 healthy volunteers using the technique of gamma-scintigraphy. The labelling process was dependent on the method of separation of free and liposomally bound activity and on the concentration of stannous chloride (SnCl2) used. Gel chromatography resulted in lower labelling efficiencies on increased SnCl2 concentration due to the progressive failure of liposomes to elute from the column. Higher labelling efficiencies were achieved following treatment with an anionic exchange resin as a result of efficient recovery of the liposomes. Transmission electron microscopy and X-ray microanalysis showed that liposomes (1 ml containing 40 mg phospholipid) labelled with 20–25 MBq 99mTc in the presence of 0.3 mg SnCl2 appeared uncontaminated with technetium-tin colloid, and were used in the in vivo studies. Pulmonary deposition of multi-lamellar and small unilamellar vesicles, delivered from an air jet nebulizer, was dependent on droplet size of the aerosol product. Short term clearance of both liposome populations was typical of muco-ciliary transport resulting in statistically equivalent retentions at 6 h. Subsequent retention data suggested that faster process(es) than those described for insoluble particulates were contributing to the clearance of alveolar deposited liposomes. |
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Keywords: | liposomes gamma-scintigraphy human pulmonary deposition pulmonary clearance |
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