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Abstract

Evaluation of cationized rat albumin as a potential blood-brain barrier drug transport vector.

W M Pardridge, D Triguero, J Buciak and J Yang
Journal of Pharmacology and Experimental Therapeutics November 1990, 255 (2) 893-899;
W M Pardridge
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D Triguero
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J Buciak
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J Yang
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Abstract

The present investigations evaluated the effects in rats of repetitive administration of cationized rat albumin over an 8-week period with the future aim of using this modified protein as a vector to transport drugs across the brain capillary endothelial wall, i.e., the blood-brain barrier. Rat albumin was cationized at pH = 7.8 with hexamethylenediamine, and the isoelectric point of the protein was raised from 5.5 to approximately 8. The cationized protein was monomeric based on mobility during sodium dodecylsulfate polyacrylamide gel electrophoresis. After radiolabeling, the cationized rat serum albumin (RSA) was taken up by isolated rat or bovine brain microvessels, whereas radio-labeled native RSA was not taken up by the capillaries in vitro. The brain volume of distribution of the 3H-cationized RSA increased linearly over a 5-hr period after an intravenous injection of the isotope and reached a value of 46 +/- 3 microliter/g (mean +/- S.E.) by 5 hr, whereas the brain volume of distribution of the 125I-native RSA was constant during the 5-hr time period (9.3 +/- 0.7 microliter/g, which is equal to the brain blood volume). The cationized and native RSAs were administered daily (Monday through Friday) at a dose of 1 mg/kg subcutaneously to groups of rats for 4- and 8-week periods. This dosage regimen resulted in no discernible toxicity, based on the findings of normal weight gain, normal tissue histology and normal serum chemistry. Therefore, cationized rat albumin may be used in future studies that use the repetitive administration of cationized rat albumin chimeric peptides for the evaluation of the transport of these substances through the blood-brain barrier in vivo.

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Journal of Pharmacology and Experimental Therapeutics
Vol. 255, Issue 2
1 Nov 1990
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Abstract

Evaluation of cationized rat albumin as a potential blood-brain barrier drug transport vector.

W M Pardridge, D Triguero, J Buciak and J Yang
Journal of Pharmacology and Experimental Therapeutics November 1, 1990, 255 (2) 893-899;

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Abstract

Evaluation of cationized rat albumin as a potential blood-brain barrier drug transport vector.

W M Pardridge, D Triguero, J Buciak and J Yang
Journal of Pharmacology and Experimental Therapeutics November 1, 1990, 255 (2) 893-899;
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