摘要 |
A second generation of antineoplaston therapies with markedly improved antineoplastic activity is disclosed. Among others, members of the antineoplaston family include phenylacetate (PN), 3-phenylacetyl-amino-2,6, piperidinedione (CN), and hydrolysis derivatives of CN: phenylacetylglutamine (PG) and iso-phenylacetylglutamine (Iso-PG). In part, these increases in antineoplastic activity result from large increases in the transport of antineoplaston compositions into cells. Importantly and unexpectedly these increases in antineoplastic activity also result from the capacity of the drug delivery system to direct antineoplaston compounds intracellular trafficking to intracellular binding sites influencing cell viability and proliferation. Liposomal formulations of antineoplaston compositions increase in vitro antineoplastic activity by a factor of 750 to 1500 as compared to administration of antineoplaston compounds given without liposomal formulations. In addition, these liposomal formulations enhanced cellular uptake of antineoplaston compounds form 30 to more that 80 fold. Liposomal formulations were also fou nd to increase intracellular levels of the antineoplaston CN(3-phenylacetyl-amino-2,6, piperidinedione) by directing CN to intracellul ar binding sites that influence cell viability and proliferation and block its hydrolysis. Under conditions where free CN has no antineoplast ic activity, liposomally formulated CN can produce essentially complete and relatively long-lasting blockade of cell growth. Ce ll growth was found to be restored as intracellular levels of bound CN decrease to undetectable levels.
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