In vivo transport and pharmacokinetic behavior of tumour photosensitizers

Abstract

The mechanisms by which photodynamic sensitizers are transported in the bloodstream influence their distribution among normal and tumour tissues, as well as their partitioning among the various compartments of tumour tissues. Column chromatographic analysis and density gradient ultracentrifugation of sera obtained from both patients and experimental animals show that hydrophilic photosensitizers (e.g. haematoporphyrin, and tetrasulphonated porphyrins and phthalocyanines) are largely transported by albumin and globulins and mainly deposited in the vascular stroma of tumours. More hydrophobic photosensitizers (haematoporphyrin oligomers, porphyrin esters, monosulphonated or unsubstituted phthalocyanines) are preferentially incorporated in the lipid core of lipoproteins. Tightly aggregated dyes partly circulate as unbound pseudomicellar structures which can be entrapped in the interstitial regions of the tumour, localize in macrophages, or enter neoplastic cells via pinocytotic processes. Low density lipoproteins (LDL), which are endocytosed by neoplastic cells through a specific receptor-mediated pathway, display the most selective release of photosensitizers to tumours. The binding of the injected photosensitizer to LDL can be enhanced by preincorporation of the dye in liposomal vesicles which are in a quasi-solid state at the body temperature.