mTHPC Polymer Conjugates: The In Vivo Photodynamic Activity of Four Candidate Compounds

Abstract.

The in vivo photodynamic activities of four poly(ethylene glycol) (PEG) conjugates of the photosensitiser 5,10,15,20-tetrakis-(m-hydroxyphenyl)chlorin (mTHPC, temoporfin, Foscan^®) were compared with that of mTHPC over a range of drug–light intervals using acute tumour necrosis and skeletal muscles swelling in a mouse model in order to ascertain the influence of linking group stability and PEG chain length on the photodynamic activity. The four compounds examined contained either PEG 2000 or PEG 5000 attached by carbonate or triazine linkages at the phenol hydroxyl groups of the mTHPC.

All compounds tested caused tumour necrosis at drug–light intervals of between one and four days. mTHPC produced tumour necrosis of over 5 mm at drug–light intervals of 1 and 2 days with limited muscle damage at early drug–light intervals. The relatively labile carbonate-linked conjugates gave tumour necrosis similar to mTHPC but produced severe muscle and systemic phototoxicity on irradiation at 4–24 h after injection. The more stable triazine-linked conjugates produced no significant muscle damage at any of the drug–light intervals tested, but gave only limited tumour necrosis under the conditions tested. PEG chain length had relatively little effect on the patterns of bioactivity.

It is concluded that both classes of mTHPC PEG conjugates may be suitable for photodynamic therapy if the problems of stability and early photosensitivity in the case of the carbonates and reduced potency in the case of the triazines can be overcome through improved formulations and PDT treatment regimens.