Synthesis and in Vivo Antitumor Activity of Poly(l-glutamic acid) Conjugates of 20(S)-Camptothecin

Abstract
Poly-α-(l-glutamic acid) (PG) conjugates of 20(S)-camptothecin (1, CPT) displayed improved aqueous solubility compared to CPT, were stable in aqueous solution at neutral pH, and were potent antitumor agents in vivo. Evaluation of PG molecular weight, CPT loading, aqueous solubility, and CPT equivalent dosing with respect to in vivo antitumor potencies of various linked conjugates led to identification of a preferred conjugate composition.