mTHPC polymer conjugates: The in vivo photodynamic activity of four candidate compounds

The in vivo photodynamic activities of four poly(ethylene glycol) (PEG) con jugates of the photosensitiser 5,10,15,20-tetrakis-(m-hydroxyphenyl)chl (mT HPC, temoporfin, Foscan(R)) were compared with that of mTHPC over a range o f drug-light intervals using acute tumour necrosis and skeletal muscles swe lling in a mouse model in order to ascertain the influence of linking group stability and PEG chain length on the photodynamic activity. The four comp ounds 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 betw een 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-li ght intervals. The relatively labile carbonate-linked conjugates gave tumou r necrosis similar to mTHPC but produced severe muscle and systemic phototo xicity on irradiation at 4-24 h after injection. The more stable triazine-l inked conjugates produced no significant muscle damage at any of the drug-l ight intervals tested, but gave only limited tumour necrosis under the cond itions tested. PEG chain length had relatively little effect on the pattern s of bioactivity. It is concluded that both classes of mTHPC PEG conjugates may be suitable f or photodynamic therapy if the problems of stability and early photosensiti vity in the case of the carbonates and reduced potency in the case of the t riazines can be overcome through improved formulations and PDT treatment re gimens.