A horseradish peroxidase-light and electron microscopic study of immunoliposomes utilized for intracellular delivery to the rat striatum.
Liposomes can deliver plasmid DNA, viruses, antisense oligonucleotides, and pharmacological agents to the central nervous system. Conjugation of antibodies to liposomes increases delivery specificity. Immunoliposomes created with Thy 1.1 antibody have previously been shown to be effective for neuronal delivery. The intracellular delivery of these immunoliposomes is evaluated by light and electron microscopy. Thy 1.1 conjugated liposomes were loaded with horseradish peroxidase and stereotactically injected into rat striatum. On light microscopy, immunoliposomes were concentrated within 0.2 mm of the injection site 8 h following delivery but, 24 h post-operatively, had diffused more than 0.5 mm from the injection site. With transmission electron microscopy, immunoliposomes were observed entering numerous neurons and some astrocytes in a process distinct from the clathrin-coated pit mechanism. These findings suggest that Thy 1.1 immunoliposomes are effective for intracellular delivery in vivo and their endocytosis occurs independently of a coated pit process. The research has helped to elucidate alternative mechanisms for immunoliposomal delivery. A more fundamental understanding of these attributes is needed to achieve the therapeutic potential of immunoliposomes.
Sheehan
J P
JP
Department of Neurological Surgery, University of Virginia, Charlottesville, VA 22908, USA. jps2f@virginia.edu
Sheehan
J M
JM
Holmberg
E G
EG
Geisert
E E
EE
Helm
G A
GA
D000818:Animals; D003342:Corpus Striatum / Q000378:metabolism / Q000648:ultrastructure*; D004337:Drug Carriers; D016503:Drug Delivery Systems; D006735:Horseradish Peroxidase / Q000378:metabolism; D018796:Immunoconjugates; D008081:Liposomes / Q000276:immunology / Q000493:pharmacokinetics; D008854:Microscopy, Electron / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018800:Thy-1 Antigens; D013997:Time Factors; D014018:Tissue Distribution
D004337:Drug Carriers; D018796:Immunoconjugates; D008081:Liposomes; D018800:Thy-1 Antigens; D006735:Horseradish Peroxidase