LIPOSOMAL ANTINEOPLASTON THERAPIES WITH MARKEDLY IMPROVED ANTINEOPLASTIC ACTIVITY

摘要

A second generationof antineoplaston therapieswith markedly improvedantineoplastic activity isdisclosed. Among others,members of the antineoplastonfamily include phenylacetate(PN), 3-phenylacetyl-amino-2,6,piperidinedione (CN), andhydrolysis derivatives of CN:phenylacetylglutamine (PG)and iso-phenylacetylglutamine(Iso-PG). In part, theseincreases in antineoplasticactivity result from largeincreases in the transport ofantineoplaston compositionsinto cells. Importantly andunexpectedly these increasesin antineoplastic activity alsoresult from the capacity of thedrug delivery system to directantineoplaston compoundsintracellular trafficking to intracellular binding sites influencing cellviability and proliferation. Liposomal formulations of antineoplastoncompositions increase in vitro antineoplastic activity by a factor of 750 to1500 as compared to administration of antineoplastoncompounds given without liposomal formulations. In addition, these liposomalformulations enhanced cellular uptake of antineoplastoncompounds form 30 to more that 80 fold. Liposomal formulations were also foundto increase intracellular levels of the antineoplastonCN(3-phenylacetyl-amino-2,6, piperidinedione) by directing CN to intracellularbinding sites that influence cell viability and proliferationand block its hydrolysis. Under conditions where free CN has no antineoplasticactivity, liposomally formulated CN can produceessentially complete and relatively long-lasting blockade of cell growth. Cellgrowth was found to be restored as intracellular levels ofbound CN decrease to undetectable levels.