Drug delivery is an important field of nanomedicine, and its aim is to deliver specific active substances to a precise site of action in order to produce a desired pharmacological effect. In the present study nanocapsules were obtained by a process of interfacial condensation between chitosan (dissolved in the aqueous phase) and poly(N-vinyl pyrrolidone-alt-itaconic anhydride), a highly reactive copolymer capable of easily opening the anhydride ring under the action of amine groups of chitosan. The formed amide bonds led to the formation of a hydrogel membrane. The morphology of the obtained nanocapsules, their behavior in aqueous solution of physiological pH, and their ability to encapsulate and release a model drug can be modulated by the parameters of the synthesis process, such as the molar ratio between functional groups of polymers and the ratio of the phases in which the polymers are solubilized. Although a priori both polymers are biocompatible, this paper reports the results of a very detailed in vivo study conducted on experimental animals which have received the obtained nanocapsules by three administration routes—intraperitoneal, subcutaneous, and oral. The organs taken from the animals’ kidney, liver, spleen, and lung and analyzed histologically demonstrated the ability of nanocapsules to stimulate the monocytic macrophage system without producing inflammatory changes. Moreover, their in vivo behavior has been shown to depend not only on the route of administration but also on the interaction with the cells of the organs with which they come into contact. The results clearly argue the biocompatibility of nanocapsules and hence the possibility of their safe use in biomedical applications.