Abstract:
:A liposomal formulation of UCN-01 was studied to prevent binding of drug to human alpha1-acid glycoprotein (hAGP). The release of drug from liposomes added to various media was investigated by monitoring the concentration of UCN-01 in different fractions. Protein bound UCN-01 was separated from liposomal UCN-01 and free UCN-01 by gel chromatography and the drug content in the fractions was measured by high-performance liquid chromatography. Also, the blood levels of hAGP bound drug and drug retained in liposomes were assessed after intravenous administration to rats of UCN-01 liposomes together with hAGP. In media containing hAGP, but not rat AGP, UCN-01 was released from liposomes. When UCN-01 liposomes were mixed with rat plasma plus hAGP, the UCN-01 in the liposomes was only gradually released so that some drug remained in the liposomes, and therefore not bound to hAGP, for up to 24 h. After the mixture of liposomal UCN-01 and hAGP was injected into rats, some UCN-01 was retained in liposomes for several hours. Encapsulation of UCN-01 into liposomes is an effective method of preventing binding of UCN-01 to hAGP.
journal_name
Biol Pharm Bulljournal_title
Biological & pharmaceutical bulletinauthors
Yamauchi M,Kusano H,Nakakura M,Kato Ydoi
10.1248/bpb.28.1259subject
Has Abstractpub_date
2005-07-01 00:00:00pages
1259-64issue
7eissn
0918-6158issn
1347-5215pii
JST.JSTAGE/bpb/28.1259journal_volume
28pub_type
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