The controlled delivery of low-molecular weight drugs and proteins from biodegradable polymers has received considerable attention. However, controlled release studies of pDNA from such polymers have not been reported to date. In this study, a plasmid DNA was complexed with the cationic polymer called polyethylenimine (PEI). This gene vector has been shown to be very effective in transfecting cells. The complexed DNA were then incorporated into different types of poly-lactic-co-glycolic acid (PLGA) film; PLGA 53/47 (M-w 90 kDa), 50/50 (M-w 11 kDa, end group is lauryl ester) and 75/25 (M-w 120 kDa). Their release profiles from a buffer solution were studied. An initial (small) burst release of PEI-DNA from film was observed in PLGA 53/47 and 50/50, followed by a plateau phase and finally a rapid erosion-controlled release. For PLGA 50/50, the rapid release started after 14 days; erosion-controlled release for PLGA 53/47 started after 9 days; for PLGA 75/25, the release rate was governed by an initial burst release (10%) followed by a slow release controlled by diffusion. No obvious erosion-controlled release rate was observed for this polymer up to 27 days. Thus, the controlled release of complexed DNA follows the general features exhibited by lower- M-w drugs. This is of significance in designing gene vector matrices that offer the promise of more lasting gene therapy compared with particulate formulations. (C) 2008 Wiley Periodicals, Inc.