Poly(D,L-lactide-co-glycolide) (PLGA) and poly(ethylenimine) (PEI) were blended and found to form a homogeneous pH sensitive matrix for drug release. Differential scanning calorimetry (DSC) studies of the PLGA/PEI blends showed a single glass transition temperature at all compositions. Fourier transform infrared spectroscopy (FTIR) demonstrated that the PLGA carbonyl peak at 1760 cm(-1) shifted to 1666 cm(-1) as a result of amide bond formation between the two polymers. This was confirmed by C-13 nuclear magnetic resonance studies. A PLGA/PEI matrix of 90/10 weight ratio was chosen for evaluation for controlled drug release. Both hydrophobic P-lapachone and hydrophilic rhodamine B showed pH dependent release profiles with faster release kinetics at lower pH values. The observed pH sensitive drug release was mainly attributed to two factors, pH dependent swelling and protonation of the PEI-PLGA matrix. These results demonstrate utility of a PLGA/PEI matrix and its potential application in pH responsive drug delivery. (c) 2006 Wiley Periodicals, Inc.