A new aqueous nanoparticle system has been developed using complex coacervation employing the oppositely charged polymers polyethylenimine (PEI) and dextran sulfate (DS), with zinc sulfate as a stabilizing agent. Amphotericin B (AmB) was loaded into the nanoparticles as a model drug. The nanoparticles contained PEI and DS in the weight ratio of $1:2. They possessed a zeta potential of approximately 30 mV and demonstrated a narrow size distribution in the range 100±600 nm with a polydispersity index of 0.2. Electron microscopy revealed spherical nanocapsules with a smooth surface. Very favorable drug entrapment and recovery ef®ciencies of up to 85% were routinely observed. Processing parameters, such as the pH of the PEI solutions, ratio of the two polymers, as well as the concentrations of DS and zinc sulfate, all played a signi®cant role in controlling particle size. Dissolution studies demonstrated a fast release that is dependent on the model drug solubility. The AmB-loaded nanoparticles displayed no toxicity in tissue culture in contrast to free drug and were almost as ef®cacious as free drug in killing Candida albicans. Advantages of this simple technique are (1) ease of manufacturing and mild preparation conditions, (2) employment of completely aqueous processing conditions, (3) use of biocompatible polymers that can be prepared aseptically, (4) ability to control their size, and (5) a high level of drug entrapment.