Poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) copolymeric microparticles (MPs) and nanoparticles (NPs) were prepared by the double-emulsion solvent-evaporation technique. 5-Fluorouracil (5-Fu), an anticancer drug, was entrapped in PHBHHx NPs and MPs. A variety of parameters, including the species and concentration of different surfactants, power and time of ultrasonication for particle dispersion, and organic/aqueous solution ratio, that affected the production of the 5-Fu-loaded PHBHHx NP and MP particles and the release of 5-Fu were studied. The results show that the prepared NPs and MPs were spherical in shape and about 160 nm and 3 mu m in size, respectively, when cetyltrimethyl ammonium bromide was used as the emulsifier. The drug-loading content (DLC) varied from 3.53 to 8.03% for 5-Fu-loaded NPs and from 4.83 to 18.87% for 5-Fu-loaded MPs and depended on the different initial feeding amounts of 5-Fu. The encapsulation efficiency decreased with increasing DLC. The in vitro drug-release characteristics appeared to have two phases with an initial burst effect occurring within the first 8 h; this was more obvious for the particles with low DLCs. The NPs with high DLC (8.03%) had the slowest release rate, 49.6% of 5-Fu within 24 h. Therefore, PHBHHx copolymeric NPs and MPs can possibly be applied as drug-delivery carrier materials in the future. (C) 2010 Wiley Periodicals, Inc. J Appl Polym Sci 116: 2944-2950, 2010