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Poor drug encapsulation efficiency and rapid release of the encapsulated drug limit the use of nanoparticles in biomedical applications involving water‐soluble drugs. We have developed a novel polymer‐surfactant nanoparticle formulation, using the anionic surfactant Aerosol OT™ (AOT) and polysaccharide polymer alginate, for sustained release of water‐soluble drugs. Particle size of nanoparticles, as determined by atomic force microscopy and transmission electron microscopy, was in the range of 40–70 nm. Weakly basic molecules like methylene blue, doxorubicin, rhodamine, verapamil, and clonidine could be encapsulated efficiently in AOT‐alginate nanoparticles. In vitro release studies with basic drug molecules indicate that nanoparticles released 60–70% of the encapsulated drug over 4 weeks, with near zero‐order release during the first 15 days. Studies with anionic drug molecules demonstrate poorer …