Tumor accumulation of poly(ethylene glycol) with different molecular weights after intravenous injection

Body distribution of poly(ethylene glycol) (PEG) with different molecular weights (MWs) was investigated after intravenous injection into mice with a tumor mass of their back subcutis and footpad to evaluate the effect of PEG molecular weight on the tumor accumulation. PEG did not exhibit specific affinity for any organs and PEG with higher MW tended to remain in the blood circulation of tumor-bearing mice longer than PEG with lower MW, similarly to normal mice. PEG accumulated at the tumor tissue to a significantly higher extent than at the normal tissue, irrespective of the molecular weight and the tumor loading site. Such high tumor accumulation of PEG increased with an increase in the size of the tumor mass, leveling off at a certain size. This size dependence was in accord with that of the vasculature volume in the tumor tissue. Because PEG extravasates to the interstitial space of the tumor, the tumor accumulation seems to be governed mainly by the level of hyperpermeable vasculature. The PEG molecules accumulated at the tumor tissue were retained longer than those at the normal tissue, The tumor accumulation of PEG became maximal at MW around 200,000. A pharmacokinetic study demonstrated that the accumulation rate of PEG at the tumor tissue was higher than that at the normal tissue and decreased with increasing molecular weight. On the other hand, the higher the molecular weight of PEG, the longer the retention time in the blood circulation. It is likely that the balance between these two factors, the accumulation rate of PEG and the blood retention, results in maximal accumulation of PEG with a medium molecular weight.