EFFECT OF AXIAL LIGATION AND DELIVERY SYSTEM ON THE TUMOR-LOCALIZING AND TUMOR-PHOTOSENSITIZING PROPERTIES OF GE(IV)-OCTABUTOXY-PHTHALOCYANINES

Four Ge(IV)-octabutoxy-phthalocyanines (GePcs) bearing two alkyl-type axial ligands were assayed for their pharmacokinetic properties and ph ototherapeutic efficiency in Balb/c mice bearing an intramuscularly tr ansplanted MS-2 fibrosarcoma. The GePcs were i.v. injected at a dose o f 0.35 mu mol kg(-1) body weight after incorporation into either Cremo phor emulsions or small unilamellar liposomes of dipalmitoyl-phosphati dylcholine (DPPC). Both the nature of the delivery system and the chem ical structure of the phthalocyanine were found to affect the behaviou r of the GePcs in vivo. Thus, Cremophor-administered GePcs invariably yielded a more prolonged serum retention and a larger association with low-density lipoproteins (LDLs) as compared with the corresponding li posome-delivered phthalocyanines. This led to a greater efficiency and selectivity of tumour targeting. These effects were more pronounced f or those GePcs having relatively long alkyl chains (hexyl to decyl) in the axial ligands. Maximal tumour accumulation (0.67 nmol per g of ti ssue) was found for Ge-Pc(hexyl), at 24 h after injection. Consistentl y, the Ge-Pc(hexyl),, administered via Cremophor, showed the highest p hototherapeutic activity towards the MS-2 fibrosarcoma.