ENHANCED INTESTINAL-ABSORPTION OF AN RGD PEPTIDE FROM WATER-IN-OIL MICROEMULSIONS OF DIFFERENT COMPOSITION AND PARTICLE-SIZE

被引:67
作者
CONSTANTINIDES, PP [1 ]
LANCASTER, CM [1 ]
MARCELLO, J [1 ]
CHIOSSONE, DC [1 ]
ORNER, D [1 ]
HIDALGO, I [1 ]
SMITH, PL [1 ]
SARKAHIAN, AB [1 ]
YIV, SH [1 ]
OWEN, AJ [1 ]
机构
[1] IBAH INC,BIOPHARM DRUG DELIVERY SERV,ASTON,PA 19014
关键词
WATER-IN-OIL MICROEMULSION; LIPID COMPOSITION; PARTICLE SIZE; INTESTINAL ABSORPTION; FIBRINOGEN RECEPTOR ANTAGONIST; PHARMACOKINETICS;
D O I
10.1016/0168-3659(94)00129-I
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
The fibrinogen receptor antagonist SK and F 106760 is a water-soluble tetrapeptide (M(r) 634) with very low oil/water partitioning and membrane permeability. Thus, the intraduodenal bioavailability of this peptide in the rat from a saline formulation was found to be less than 1%. Upon formulation, however, in w/o microemulsions of different composition and particle size, the intraduodenal bioavailability of SK and F 106760 was increased up to 29% depending on the microemulsion composition. There was no apparent correlation between the particle size of microemulsions (mean droplet diameter of 0.010-1.0 mu m) and enhanced absorption. None of the investigated microemulsions induced gross changes in gastrointestinal mucosa at a dosing volume of 3.3 ml/kg. Lipids containing medium-chain fatty acids play a major role on the observed absorption enhancement. These findings further support the use of microemulsion formulations for oral drug/peptide delivery, provided however, that development issues with these systems are properly addressed.
引用
收藏
页码:109 / 116
页数:8
相关论文
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