This work describes the preparation and characterization of anticancer‐loaded injectable polymeric depots that consisted of d,l‐lactide (LA), ε‐caprolactone (CL), and poly(ethylene glycol) (PEG) or [poly(ε‐caprolactone)‐random‐poly(d,l‐lactide)]‐block‐poly(ethylene glycol)‐block‐[poly(ε‐caprolactone)‐random‐poly(d,l‐lactide)] (PLEC) copolymers for malignant gliomas treatment. PLECs were polymerized with different percentages of LA to deliver 7‐ethyl‐10‐hydroxycamptothecin (SN‐38), a highly potent anticancer drug. SN‐38‐loaded depots could form directly in phosphate buffer saline with more than 98% encapsulation efficiency. The release rate of SN‐38 from depots was found to depend on the amount of LA in PLECs, loading content of SN‐38 in the depots, and depot weight. Encapsulation of SN‐38 inside depots could enhance the stability of SN‐38 where all of SN‐38 released after 60 days was in an active form. Depots without SN‐38 were evaluated as noncytotoxic against U‐87MG, whereas SN‐38‐loaded depots showed cytotoxic effect as a function of concentration. © 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101:3708–3717, 2012