Properties of stearylamine liposomes containing tyrosine phenol-lyase |
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Authors: | Herbert F. Pierson Gary G. Meadows |
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Affiliation: | College of Pharmacy, Washington State University, Pullman, WA 99164, U.S.A. |
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Abstract: | The activity of tyrosine phenol-layse a chemotherapeutic enzyme with a dissociable pyridoxal phosphate cofactor, was studied after incorporation into multilamellar positively charged liposomes. Tyrosine phenol-lyase activity was assessed in the presence and absence of exogenous pyridoxal phosphate. A maximum of 75% total enzyme activity was associated with liposomes when prepared from a molar lipid ratio of egg lecithin, cholesterol, stearylamine (7 : 2 : 1, w/w). The total tyrosine phenol-lyase activity was comprised of 25% membrane-associated enzyme and 50% encapsulated enzyme. Encapsulation increased the stability of the enzyme under the in vitro conditions of cold storage at 4°C for 3 weeks and under elevated temperatures up to 61°C. Liposomal encapsulation afforded little protection against trypsin and no protection against whole mouse plasma in vitro. Heat-treated plasma (100°C for 1 h) had little effect on the activity of free and encapsulated tyrosine phenol-lyase. These results indicated that whole plasma contained a heat-labile factor(s) which destroyed both the liposomal and free tyrosine phenol-lyase activity. Plasma clearance after intraperitoneal injection of tyrosine phenol-lyase in B6D2F1 female mice was reduced by liposomal encapsulation, particularly when the animals were pre-treated with empty liposomes; however, only a small proportion of free and liposomal tyrosine phenol-lyase was absorbed. The free enzyme rapidly lost holoenzyme activity after absorption but the liposomes maintained holoenzyme activity. Even though liposomes preserved holo-tyrosine phenol-lyase activity, the holoenzyme was not present in sufficient concentration to sustain a reduced plasma tyrosine level. |
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Keywords: | Stearylamine Pyridoxal phosphate Liposome stability Tyrosine phenol-lyase |
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