A prospective approach was used to synthesize carbohydrate nanocapsules with a macromolecule payload and suitable interfacial properties for in vivo systemic circulation. Spatially directed carbohydrate assembly and polymerization resulted in structured hydrophilic vesicles with diameters of 200-300 nm. Mononucleated dispersions with monodisperse distributions were demonstrated in aqueous vehicles. The effects of pH, buffer capacity and reaction time on the molar degree of substitution of terephthaloyl chloride, trimesoyl chloride, and diethylmalonyl chloride were evaluated. The delivery of a test protein, lysozyme showed continuous release for 7 days. Immobilization of lysozyme caused by co-polymerization was 20% based on asymptotic recovery of released lysozyme. A theoretical shell thickness of 9.5 nm was estimated from a relative core volume of 80% and the average vesicle size.