A series of oleamide derivatives, (C18H34NO)(2)(CH2)(n) [n = 2 (1a), 3 (1b), 4 (1c), or 6 (1d); C18H34NO = oleic amide fragment] and (C18H34NO)(CH2)(6)NH2 (2), have been synthesized and their self-assembly is investigated in ethanol/water media. Self-assembly of 1a and 1b in ethanol/water (1/0.1 v/v) solution (5 mg mL(-1)) yields microspheres (MSs) with the average diameter similar to 10 mu m via a gradual temperature reduction and solvent volatilization process. Under the same self-assembly conditions, microrods (average diameter similar to 6 mu m and several tens of micrometers in length), micronecklace-like, and shape-irregular microparticles are formed from the self-assembly of 1 c, id, and 2, respectively. The kinetics of evolution for their self-assemblies by dynamic light scattering technique and in situ observation by optical microscopy reveals that the microstructures formation is from a well-behaved aggregation of nanoscale micelles induced by solvent volatilization. The FT-IR and temperature-dependent H-1-NMR spectra demonstrate the hydrogen bonding force and pi-pi stacking, which drove the self-assembly of all oleamide derivatives in ethanol/water. Among the fabricated microstructures, the MSs from 1a exhibit the best dispersity, which thus have been used as a scaffold for the in vitro release of doxorubicin. The results demonstrate a pH-sensitive release process, enhanced release specifically at low pH 5.2.