Cyclodextrin-PEG hydrogels were prepared by reaction of hexamethlyene isocyanate-activated beta-cyclodextrins with 1.9kDa NH(2)PEGNH(2). The reaction was carried out in anhydrous dimethylsulfoxide by using 0.25:1, 0.33:1, 0.5:1, 0.67:1, 1:1, and 2:1 CD/PEG molar ratios. The addition of acetic acid to the reaction mixture was found to slow the cross-linking reaction, yielding homogeneous matrices. The mechanical characterization indicated that the elasticity of the matrices increased as the CD content in the hydrogel increased while the elongation was irrespective of the hydrogel composition. By incubation in water and ethanol, the hydrogels underwent complete swelling in 5-10min. The water up-take increased logarithmically as the CD/PEG ratio decreased to reach a swelling degree of 800% (swollen hydrogel/dry hydrogel, w/w%). The ethanol uptake increased with a power correlation as the CD/PEG ratio decreased to reach a swelling degree of about 1000% with 0.25:1 CD/PEG hydrogel. Lysozyme, beta-estradiol, and quinine were loaded by swell embedding. The lysozyme loading increased as the CD/PEG ratio decreased while the incorporation of beta-estradiol and quinine displayed inverse correlation with respect to the CD/PEG ratio. The maximal incorporation (loaded drug/dry hydrogel, w/w%) for lysozyme, beta-estradiol and quinine was 2, 0.6, and 2.4%, respectively. Lysozyme was quickly released from the matrices, and the release was faster as the CD/PEG ratio decreased. Also, beta-estradiol and quinine release rates were inversely proportional to the CD/PEG ratio, but in these cases, the release profiles were strongly affected by the drug interaction with the hexamethylated beta-cyclodextrins in the matrices.