Introduction: Tumor vasculature has enhanced permeability regulated by factors such as VEGF and MMPs [2] with a pore cut-off size of 400 nm [3]. Due to the absence of an well-defined functioning lymphatic network, the clearance of macromolecules from the interstitial compartment is seriously compromised. This results in the accumulation of molecules with a molecular weight above 50 kDa in the interstitium and an outward convective interstitial flow. Bioresorbable nanoparticles are especially attractive as a delivery system because they can be degraded by hydrolysis or enzymatic pathways to low molecular weight compounds, thereby reducing the accumulation of nanoparticles in the interstitium. Our laboratory has developed novel bioresorbable macromers that self-assemble into nanoparticles in the aqueous medium. The macromer, hereafter abbreviated by PLGEOF, contains short lactide-co-glycolide (LG) and ethylene oxide (EO) blocks linked by fumaric acid units. After self-assembly, these nanoparticles can be crosslinked or grafted with cell-responsive biomolecules for targeted delivery of antitumor drugs. The objective of this study was to determine the size distribution, degradation profile, and release characteristics of the PLGEOF nanoparticles. Methods: A 10% w/w solution of the macromers in dimethyl sulfoxide (DMSO) was dialyzed against distilled deionized (DDI) water to obtain a stable colloidal suspension of nanoparticled. The morphology of the nanoparticles was examined using a JEOL 100 CXII transmission electron microscope at an accelerating voltage of 100 kV. The size distribution of nanoparticles was measured by dynamic light scattering with a NICOMP Submicron Particle Sizer (Autodilute Model 370). Degradation was measured as a function of time in vitro in primary culture media (CM; 5 ml per sample) without fetal bovine serum (FBS) at 37°C under mild agitation. Dextran fluorescein isothiocyanate (FITC-dextran) and paclitaxel were used as surrogate molecules for release studies. Results: The size of the nanoparticles depended strongly on the ratio of PLA to PLEOF in the mixture. The 100:0 90:10, 80:20, and 60:40 ratios, had number average size of 480, 195, and 50, and 14 nm and volume average size of 1630, 670, 185, and 23 nm, respectively. The nanoparticles, with the exception of 60:40 had bimodal size distribution. There was a significant decrease in the size of the particles from 480 to 195 and 50 nm as the PLAF:PLEOF ratio was varied from 100:0 to 90:10 and 80:20. FTIC-Dextran and paclitaxel released in a period of two weeks which matched the degradation profile of the spheres. CONCLUSION: Unsaturated terpolymer of lactide, ethylene oxide, and fumaric acid (PLEOF) with lactide to ethylene oxide ratios in the 90:10 to 70:30 spontaneously self-assembled into stable nanoparticles. The lowest particles size naoparticles was produced with lactide to ethylene oxide ratio of 60 to 40 (14 nm). These nanoparticles are potentially useful as a cell-responsive targeted delivery system for anitumor drugs.