RT Journal Article
SR Electronic
T1 Antibody Mediated Lung Targeting of Long-Circulating Emulsions
JF PDA Journal of Pharmaceutical Science and Technology
JO PDA J Pharm Sci Technol
FD Parenteral Drug Association (PDA)
SP 372
OP 377
VO 50
IS 6
A1 Young K. Song
A1 Dexi Liu
A1 Kazuo Maruyama
A1 Tomoko Takizawa
YR 1996
UL http://journal.pda.org/content/50/6/372.abstract
AB Monoclonal antibody 34A, which specifically binds to a surface glycoprotein (thrombomodulin) of the pulmonary endothelial cell surface in mice, has been conjugated to the surface of long-circulating emulsions composed of Castor oil, phosphatidylcholine and polyethylene glycol coupled to distearoylphosphatidyl-ethanolamine. These antibody-containing emulsions were found capable of binding to the lung when injected into mice through the tail vein. The level of lung accumulation of these emulsions depends on the amount of antibodies conjugated to the surface of the emulsions. With an input antibody to lipid ratio of 2:1 (w/w), 30% injected emulsions were found in the lung 30 minutes after administration. Such high level accumulation can be blocked by co-administration of free 34A antibody, indicating that the binding is specific and 34A antibody mediated. Kinetic studies showed that emulsion targeting to the lung was very rapid. Five minutes after tail vein injection, the total amount of emulsion found in the lung was the highest among the time points examined, indicating the completion of lung binding. However, about 50% of the initially bound emulsions remained bound for more than 4 hours. These results indicate that the targeted drug delivery using oil-in-water emulsions could be very useful to enhance the therapeutic efficacy of lipophilic drugs.