Poly(isobutyl cyanoacrylate) nanoparticles were prepared. They were degraded in two enzyme-free media at pH 7 and 12 in the presence of rat liver microsomes. The conventional formaldehyde-producing degradation route was studied, and showed a very low efficiency. Another pathway, consisting of ester hydrolysis, was identified and studied. In contrast to the formaldehyde pathway, ester hydrolysis was shown to be catalysed by enzymes. Finally, the release rate of adsorbed actinomycin from nanoparticles was proved to correlate exactly with the degradation rate of the polymer.