Conventional marketed formulations of cyclosporine A (CsA) have considerable limitations owing to poor drug bioavailability and extensive inter- and intrapatient variability. Nanoparticles are currently used as an alternative to solve these issues, but attainment of an effective nanoformulation loaded with CsA is a significant challenge. In this study, we described the preparation and characterization of poly[methyl vinyl ether-co-maleic anhydride (PVM/MA) nanoparticles loaded with CsA and examined in vitro release of the drug from the novel formulation. Derivatives of cyclodextrin were used to improve drug loading in the nanoparticles and modulate the CsA release profile. Nanoparticles were prepared using a solvent displacement method, and characterized based on particle size, zeta potential, encapsulation efficiency, product yield, X-ray and thermal analyses. Our results showed that the nanoparticles are ~100¿243 nm in size and the amount of CsA loaded is higher when the nanoformulation contains hydroxypropyl-ß-cyclodextrin than hydroxypropyl-¿-cyclodextrin. Furthermore, these nanoparticles showed biphasic release behaviour in physiological media, consistent with characteristics of nanoparticle drug delivery systems in general. This biphasic profile indicates that CsA is released from nanoparticles through diffusion in the initial phase and subsequent time-period. The in vitro release profile of CsA from nanoformulations with hydroxypropyl-¿-cyclodextrin additionally showed a higher initial burst effect in all simulated physiological media used. Our results collectively support the potential utility of a nanoformulation with hydroxypropyl-ß-cyclodextrin in improving the bioavailability of CsA in vivo.