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Review

Biomedical aspects of targeted delivery of drugs to pulmonary endothelium

Pages 909-926 | Published online: 16 Sep 2005

Bibliography

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  • •This is the first of a series of publications from Danilov's group that established ACE as a candidate determinant for targeted drug delivery to the pulmonary endothelium. This particular study explored visualisation of pulmonary vasculattu•e by anti-ACE radio-immunoscintigraphy, a methodology that has later been successfully employed in human studies using radiolabelled anti-ACE.
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  • •This chapter summarises 10 years of research in Danilov's group focused on vascular immunotargeting to ACE, and provides an overview of massive amounts of animal data and limited results of human studies using anti-ACE, including imaging of radiolabelled anti-ACE in normal volunteers and sarcoidosis patients.
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  • •This and subsequent paper introduce the concept of retargeting of adenoviral gene therapy means to the pulmonary vasculature using hetero-conjugate consisting of anti-ACE (which directs viruses to the pulmonary endothelium) and antiviral antibody (which couples anti-ACE to virus and blocks natural viral tropism to hepatic receptors).
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  • •This and the following publications by Mum et al. describe molecular and cellular mechanisms involved in regulation of endothelial endocytosis and subsequent intracellular traffic of cargos internalised by CAM-endocytosis induced by multivalent binding of drug carriers to constitutively non-intemalisable cell adhesion molecules ICAM-1 and PECAM–1.
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  • •This and other works from Gimbrone's group provided rationale for exploration of endothelial E-selectin as a determinant for selective delivery of drugs to vascular areas involved in inflammation and thrombosis.
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  • •This animal study is one of the first of a large group of publications that explores potential utility of inducible endothelial cell adhesion molecules as targets for visualisation of sites of inflammation and pathological activation of vascular endothelium.
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  • •This paper introduces a strategy for targeting specific surface determinants localised in rat pulmonary vasculature in endothelial caveoli. In addition to enhanced effectiveness of drug delivery to pulmonary endothelial cells attained after Intravenous injection in rats, targeting caveoli facilitates internalisation of endothelium-bound materials and their transcellular traffic via a unique endocytotic pathway.
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  • •This paper, from one of the leading groups in the area of endothelial endocytosis and traffic via caveoli, describes facilitation of these mechanisms by chemically modified ligands of caveolar determinant, a paradigm potentially useful for pulmonary vascular drug delivery.
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