Blood and tissue levels of elemental
platinum (Pt) were measured after the administration of a liposomally entrapped
cisplatin analogue, cis-bis-neodecanoato-trans-R,R-1,2-diaminocyclohexane
platinum (II) (
L-NDDP). In mice bearing subcutaneous
B16 melanoma tumors, Pt
tumor levels were not significantly different in animals treated i.v. with an equimolar dose of
L-NDDP or
cisplatin. In rabbits bearing liver
tumors of VX2
carcinoma, i.v. administration of
L-NDDP resulted in 2- to 20-fold higher Pt levels in all tissues (including VX2
tumors) except the brain and peripheral nerve than in animals treated with an equimolar dose of
cisplatin. Compared with i.v. administration, inoculation of either
drug into the proper hepatic artery resulted in a severalfold increase of Pt levels in the VX2
tumors. Blood and other tissue levels were not substantially changed by intraarterial (i.a.) administration. These studies show that (1) multilamellar
lipid vesicles can adequately deliver a lipophilic
cisplatin analogue (NDDP) to nonphagocytic
tumors when administered i.v. and (2) the inoculation of
L-NDDP into the proper hepatic artery results in higher Pt
tumor levels than with i.v. administration but does not decrease the systemic distribution of the
drug.