EFFECT OF CHEMICAL-STRUCTURE AND HYDROPHOBICITY ON THE PHARMACOKINETIC PROPERTIES OF PORPHYCENES IN TUMOR-BEARING MICE

The efficiency and selectivity of tumour targeting by several tetra-n- propylporphycene (TPPn) and tetrakis(methoxyethyl-)porphycene (TMPn) d erivatives have been studied by administering 3.76 mu mol/kg of aqueou s or liposomal porphycene formulations to BALB/c mice bearing an i.m. implanted MS-2 fibrosarcoma, These 2 parameters have been studied as a function of the type of substituents linked to the 9-position of the macrocycle by amide, ester or ether functional groups. The pharmacokin etic properties appear to be controlled mainly by the degree of porphy cene hydrophobicity, as evaluated by measuring their retention times i n a C 18 column for HPLC, Thus, the post-injection time (T-50) at whic h the porphycene concentration in the plasma decreases to 50% of the i nitial value ranged from a few minutes for the less hydrophobic to sev eral hours for the more hydrophobic porphycenes. An increase in hydrop hobicity also was accompanied by an enhanced efficiency and selectivit y of tumour targeting, The less hydrophobic porphycenes showed a maxim um tumour uptake of 0.5-2 nmol/g of tissue at 10-20 min after administ ration with a tumour/peri-tumoural concentration ratio around 2-3, whi le those with higher hydrophobicity reached tumour concentrations of 7 -8 nmol/g at 24-48 hr after administration with concentration ratios h igher than 20. (C) 1997 Wiley-Liss, Inc.