The synthesis and characterization of different series of methyl methacrylate/hydroxyethyl methacrylate (MMA/HEMA) copolymeric nanoparticles with different monomer feed compositions and utilization of them in entrapment and controlling the release of hydrophilic drug (sodium warfarin) and hydrophobic drugs (ibuprofen and praziquantel) were investigated. The polymeric nanoparticles and their entrapment with drugs were prepared using oil-in-water (O/W) differential microemulsion polymerization technique in the presence of polyvinyl pyrrolidone and polyethylene glycol as biocompatible emulsifiers as well as ammonium persulfate as an initiator. The effect of HEMA content in the monomer feed composition on the colloidal properties was studied, and it is found that the particle size Dv, turbidity, and the negative charge increase with increasing of HEMA content but the surface tension decrease. Moreover, the entrapment efficiency (EE) is affected by the content of HEMA in the monomer feed composition, the drug hydrophobicity, and the monomer to drug ratio. It is concluded that, EE into MMA/HEMA in monomer feed composition as 90/10, 70/30, and 50/50 is found to be (95.398)%, (8496.9)%, and (69.594.6)% for sodium warfarin (with high hydrophilicity) as well as, ibuprofen and praziquantel (with high hydrophobicity), respectively. The entrapment of drugs in polymeric nanoparticles is confirmed by IR-spectroscopy and transmission electronic microscopy. In vitro drug release experiments show that controlled release of drugs from copolymeric nanoparticles depend on HEMA content, the monomer to drug ratio, and the physiological pH. (c) 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 129: 853-865, 2013