Sterically stabilized
liposome is characterized by a surface coating of
polyethylene glycol (PEG) or other
polymers that can reduce opsonization of the
liposome by
plasma proteins. It has a higher plasma area under the concentration-time curve (AUC), which is believed to correlate with better therapeutic efficacy. However, the presence of large molecules on the liposomal surface may reduce the interactions of
liposomes with cells and hinder entry of
liposomes into the
tumor tissue. Using a stable liposomal system composed of
distearoyl phosphatidylcholine/
cholesterol, we examined the effect of PEG (Mr 2000) on the pharmacokinetics and on the efficacy of
liposomal doxorubicin with C-26 syngeneic
tumor model in BALB/c mice. The plasma AUC of
liposomal doxorubicin with 6 mol-% PEG-modified distearoyl
phosphatidylethanolamine (
PEG-DSPE) was approximately twice that of
liposomal doxorubicin without PEG at various dosages, regardless of whether the mice were
tumor-bearing. Paradoxically, the group of mice treated with
liposomal doxorubicin without PEG had higher
tumor doxorubicin concentrations. The 72-h
tumor AUC was 1.44 times that of
liposomal doxorubicin with 6%
PEG-DSPE. The
tumor-accumulation efficiency (AUC(
Tumor)/AUC(Plasma)) of
liposomal doxorubicin without PEG was 0.87, and this was more than twice that of the
liposomal doxorubicin with 6%
PEG-DSPE (0.31). At a dose of 10 mg/kg, although both liposomal groups were better than the free
drug group in terms of clinically relevant parameters, including toxicity,
tumor shrinkage, and survival, there was no difference between the two liposomal
drug groups. In this stable
liposome system, surface coating with PEG offered no benefit for
liposomal doxorubicin in the C-26
tumor model. To enhance the therapeutic index of
liposomal doxorubicin, simply increasing plasma AUC by surface coating with PEG may not be satisfactory.