Efficacy of camptothecin and polymer-conjugated camptothecin in tumor spheroids and solid tumors.

Camptothecin (CPT) is an anti-cancer drug with low solubility in aqueous solutions, which limits its efficacy during chemotherapy. To bypass this problem, CPT was conjugated to poly(ethylene glycol) (PEG) to make CPT more hydrophilic: CM-PEG-CPT (carboxylmethylpoly(ethlyene glycol)-camptothecin), CM-PEG-GLY-CPT (carboxylmethyl-poly(ethlyene glycol)-glycine-camptothecin) and CM-PEG-SAR-CPT (carboxylmethyl-poly(ethlyene glycol)-sarcosine camptothecin) were synthesized. These conjugates differed in the amino-acid linker, which altered the hydrolysis rate of CPT from CPT-PEG. We tested the hypothesis that CPT conjugates were more effective than unconjugated CPT in effectiveness upon direct delivery to solid tumors using two systems: in vitro tumor spheroids suspended in collagen gels and in vivo solid tumors in rats. CPT was effective in spheroids, but not in flank tumors. However, when CPT was conjugated, there was improvement in the treatment of spheroids and, to a lesser extent, tumors in rats. There was no difference in therapeutic effects among the various conjugates. We conclude that conjugation of CPT to PEG enhances CPT solubility and improves effectiveness of delivery to tumors.