Document Detail


Artificial lipids stabilized camptothecin incorporated in liposomes.
MedLine Citation:
PMID:  18451532     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Camptothecin (CPT) has anticancer activity. While only the lactone form of CPT is biologically active, this form exhibits poor aqueous solubility. Pharmaceutical formulation of CPT incorporated in liposomes is of significant importance to develop the therapeutic utilization of CPT. The aim of this study was to increase incorporation efficiency and stability of CPT in liposomes composed of hydrogenated soybean phosphatidylcholine, cholesterol, and oleic acid (7 : 3 : 1, molar ratio), by incorporating three kinds of artificial lipids (DBs) (DB-liposome); 4-n-(M12B), 3,5-bis(B12B) and 3,4,5-tris(dodecyloxy)benzoic acid (T12B). The interaction of CPT with DB in the state of liposomes, was examined. In DB-liposomes presenting mean diameters of 150 nm, incorporation efficiency of CPT up to 55% and final drug to lipid molar ratio up to 0.07 were obtained when the liposomes were prepared at a feeding ratio of 1/30 (w/w) CPT/total lipid. However, in the optimal formulations, incorporated DB mol% was different; T12B and D12B were incorporated about one third and half mol% of M12B, respectively. Moreover, we demonstrated that T12B stabilized CPT in liposomes significantly compared with other DBs as measured by CPT release, and by steady state fluorescence polarization degree of CPT using intrinsic fluorescence of CPT. These findings suggested that in addition of contribution of phenyl group of DB, dodecyloxy group may interact strongly with lactone ring of CPT. The capacity to contain CPT interacted with DBs may be limited in liposomes. T12B may be incorporated in the interior of the bilayers, resulting in increase of incorporation stability of CPT. This finding demonstrates a potential application of the novel liposome formulation of CPT in drug delivery.
Authors:
Yoshie Maitani; Sayaka Katayama; Kumi Kawano; Akihiro Hayama; Kazunori Toma
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Biological & pharmaceutical bulletin     Volume:  31     ISSN:  0918-6158     ISO Abbreviation:  Biol. Pharm. Bull.     Publication Date:  2008 May 
Date Detail:
Created Date:  2008-05-02     Completed Date:  2008-06-19     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9311984     Medline TA:  Biol Pharm Bull     Country:  Japan    
Other Details:
Languages:  eng     Pagination:  990-3     Citation Subset:  IM    
Affiliation:
Institute of Medicinal Chemistry, Hoshi University, Shinagawa-ku, Tokyo 142-8501, Japan. yoshie@hoshi.ac.jp
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MeSH Terms
Descriptor/Qualifier:
Algorithms
Anisotropy
Antineoplastic Agents, Phytogenic / chemistry*
Camptothecin / chemistry*
Drug Carriers
Excipients
Fluorescence Polarization Immunoassay
Lipids / chemistry*
Liposomes / chemistry*
Chemical
Reg. No./Substance:
0/Antineoplastic Agents, Phytogenic; 0/Drug Carriers; 0/Excipients; 0/Lipids; 0/Liposomes; 7689-03-4/Camptothecin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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