Hassan Bardania1, Seyed Abbas Shojaosadati2, Farzad Kobarfard3, Farid Dorkoosh4. 1. Department of Nanobiotechnology, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran. 2. Department of Biotechnology Group Chemical Engineering, Tarbiat Modares University, Tehran, Iran. 3. Department of Medical Chemistry, Faculty of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 4. Department of Pharmaceutics, School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
Abstract
BACKGROUND: Eptifibatide (Integrilin) is an intravenous (IV) peptide drug that selectively inhibits ligand binding to the platelet GP IIb/IIIa receptor. It is an efficient peptide drug, however has a short half-life. Therefore, antithrombotic agents like eptifibatide are required to become improved with a protected and targeted delivery system such as using nano-liposomes to the site of thrombus. OBJECTIVES: The goal in the present report was to optimize encapsulation efficiency of the eptifibatide into Arg-Gly-Asp (RGD)-modified nano-liposomes (RMNL). As well, it was intended to evaluate the effect of sodium lauryl sulfate (SLS) on drug release. MATERIALS AND METHODS: The effect of five independent variables including number of freeze/thawing cycles, concentration of eptifibatide, 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), cholesterol, and dipalmitoyl-GRGDSPA peptide on drug entrapment efficiency (DEE) was investigated using response surface methodology (RSM). The effect of different concentrations of SLS on encapsulation and drug release from RMNL was also investigated. The size and morphology of RMNL were characterized using transmission electron microscopy (TEM). RESULTS: The maximum DEE (38%) was obtained with 7 freeze/thawing cycles, 3.65 mmoL eptifibatide, 7 mM DSPC, 3 mM cholesterol, and 1 mM dipalmitoyl- GRGDSPA peptide. SLS has significantly increased the drug release from RMNL, although its effect on encapsulation efficiency was not significant. CONCLUSIONS: The optimization of the formulations for valuable and expensive peptide drugs is essential to have the maximum encapsulation efficiency and the minimum experiments.
BACKGROUND:Eptifibatide (Integrilin) is an intravenous (IV) peptide drug that selectively inhibits ligand binding to the platelet GP IIb/IIIa receptor. It is an efficient peptide drug, however has a short half-life. Therefore, antithrombotic agents like eptifibatide are required to become improved with a protected and targeted delivery system such as using nano-liposomes to the site of thrombus. OBJECTIVES: The goal in the present report was to optimize encapsulation efficiency of the eptifibatide into Arg-Gly-Asp (RGD)-modified nano-liposomes (RMNL). As well, it was intended to evaluate the effect of sodium lauryl sulfate (SLS) on drug release. MATERIALS AND METHODS: The effect of five independent variables including number of freeze/thawing cycles, concentration of eptifibatide, 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), cholesterol, and dipalmitoyl-GRGDSPA peptide on drug entrapment efficiency (DEE) was investigated using response surface methodology (RSM). The effect of different concentrations of SLS on encapsulation and drug release from RMNL was also investigated. The size and morphology of RMNL were characterized using transmission electron microscopy (TEM). RESULTS: The maximum DEE (38%) was obtained with 7 freeze/thawing cycles, 3.65 mmoL eptifibatide, 7 mM DSPC, 3 mM cholesterol, and 1 mM dipalmitoyl- GRGDSPA peptide. SLS has significantly increased the drug release from RMNL, although its effect on encapsulation efficiency was not significant. CONCLUSIONS: The optimization of the formulations for valuable and expensive peptide drugs is essential to have the maximum encapsulation efficiency and the minimum experiments.
Authors: Maximilian Schiener; Martin Hossann; Joana R Viola; Almudena Ortega-Gomez; Christian Weber; Kirsten Lauber; Lars H Lindner; Oliver Soehnlein Journal: Trends Mol Med Date: 2014-03-01 Impact factor: 11.951