This study demonstrates the effect of drug properties and method of loading (sorption and encapsulation) on entrapment within poly(alkyl cyanoacrylate) nanocapsules prepared by interfacial polymerisation of biocompatible water-in-oil microemulsions. For small molecular weight compounds ( neutral compound > anionic compound. Only minimal differences for entrapment efficiency were noted between sorption (addition of the compound 4 h after initiation of the polymerisation) and encapsulation (addition of the compound to microemulsion prior to polymerisation). For high molecular weight compounds, the method used for entrapment however, is very important. For hydrophilic macromolecules such as proteins, high entrapment efficiencies can only be achieved by encapsulation. Entrapment of such compounds seems to be independent of the net charge of the compound being encapsulated but depended on the molecular weight. For nanocapsules prepared by interfacial polymerisation of water-in-oil microemulsions, these findings are useful as a foundation in the development of nanocapsules with desired properties.