Lipoprotein delivery of benzoporphyrin derivative: A photosensitizer for photodynamic therapy

Photodynamic Therapy (PDT) involves the systemic administration of a light activated drug combined with the precise delivery of light to produce a selective cytotoxic reaction. Benzoporphyrin derivative (BPD) has been shown to be a potent photosensitizer both in vitro and in vivo and is therefore a good candidate for PDT. Since BPD is administered systemically, it is important to know the factors which affect its biodistribution. In this thesis, the in vitro and in vivo distribution of BPD in plasma was examined and the majority of BPD was recovered with the plasma lipoproteins. Association of other photosensitizers with plasma lipoproteins has been shown to increase accumulation in tumours and enhance tumour cell damage upon light activation. Based on this information, we hypothesized that association of BPD with lipoproteins, before administration, would increase the accumulation of the photosensitizer in neoplastic tissue and therefore enhance the efficacy of PDT.;In an attempt to define the mechanism by which LDL enhanced the delivery of BPD to tumours, we performed in vitro accumulation experiments using ;The effect of precomplexing BPD with purified lipoproteins on the biodistribution of the drug in vivo was studied in tumour bearing mice. Low density lipoprotein (LDL) or high density lipoprotein (HDL) associated BPD accumulated in tumour tissue in greater amounts than aqueous BPD. The association of BPD with either LDL or HDL increased tumour cell killing in vitro and the efficacy of in vivo photosensitization. In particular, LDL-BPD mixtures led to enhanced tumour eradication compared to BPD administered in aqueous solution or unfractionated plasma. These results suggest that the association of BPD with lipoproteins can have a profound effect on the eradication of tumour in vivo.