Document Detail

Long circulating emulsion carrier systems for highly lipophilic drugs.
MedLine Citation:
PMID:  8148799     Owner:  NLM     Status:  MEDLINE    
With the aim of developing of emulsion carrier systems for lipophilic drugs with the potential for prolonged circulation in the blood or hepatic targeting, the in vivo disposition of four model compounds, i.e., [3H]prostaglandin E1, [3H]retinoic acid, [14C]cholesterol, and [14C]cholesteryl oleate with calculated log PC(oct) values of 2.15, 6.61, 9.46, and 18.3, respectively, injected with various emulsion formulations, were studied in mice. Small sized emulsions of about 100 nm in diameters, with compositions of egg phosphatidylcholine (PC): soybean oil = 1:1 (small PC emulsion) and PC: egg sphingomyelin (SM): soybean oil = 0.7:0.3:1 (small SM emulsion), and a conventional emulsion with a diameter of about 250 nm and a composition of PC: soybean oil = 1:1 (large PC emulsion) were compared. Highly lipophilic [14C]cholesteryl oleate, a marker of emulsion particles, indicated diverse in vivo behaviors; i.e., the small SM emulsion produced prolonged circulation in the blood, and the small PC emulsion followed this, while the large PC emulsion was rapidly uptake by the liver. Thus, a reduction in size and coating with SM on the surface of oil droplets resulted in avoidance of the reticuloendothelial system (RES). Disposition profiles of other test compounds differed, depending on their lipophilicities: [14C]cholesterol showed disposition patterns in all formulations similar to those of [14C]cholesteryl oleate, but moderately lipophilic [3H]prostaglandin E1 and [3H]retinoic acid showed common disposition profiles, regardless of emulsion types, suggesting their rapid release from the emulsion carriers. These results suggest that small SM emulsion and large PC emulsion can act respectively as long circulating and liver targeting carriers for highly lipophilic drugs with log PC(oct) larger than 9.
T Takino; K Konishi; Y Takakura; M Hashida
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Biological & pharmaceutical bulletin     Volume:  17     ISSN:  0918-6158     ISO Abbreviation:  Biol. Pharm. Bull.     Publication Date:  1994 Jan 
Date Detail:
Created Date:  1994-05-11     Completed Date:  1994-05-11     Revised Date:  2003-11-14    
Medline Journal Info:
Nlm Unique ID:  9311984     Medline TA:  Biol Pharm Bull     Country:  JAPAN    
Other Details:
Languages:  eng     Pagination:  121-5     Citation Subset:  IM    
Department of Basic Pharmaceutics, Faculty of Pharmaceutical Sciences, Kyoto University, Japan.
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MeSH Terms
Cholesterol / blood,  pharmacokinetics*
Cholesterol Esters / blood,  pharmacokinetics
Delayed-Action Preparations
Drug Carriers*
Liver / metabolism*
Phosphatidylcholines / chemistry
Prostaglandins E / blood,  pharmacokinetics*
Soybean Oil / chemistry
Sphingomyelins / chemistry
Tissue Distribution
Tretinoin / blood,  pharmacokinetics*
Reg. No./Substance:
0/Cholesterol Esters; 0/Delayed-Action Preparations; 0/Drug Carriers; 0/Emulsions; 0/Phosphatidylcholines; 0/Prostaglandins E; 0/Sphingomyelins; 302-79-4/Tretinoin; 303-43-5/cholesteryl oleate; 57-88-5/Cholesterol; 7732-18-5/Water; 8001-22-7/Soybean Oil

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