New anti-HIV active agents, polyrotaxane-AZT conjugates with various bioactive bulky stoppers such as 3'-azido-3'-deoxythymidine (AZT) and tocopherol and their nanoparticles were synthesized and characterized. The degree of AZT substitution of the conjugates was calculated from ELEM. ANAL and ranged from 1.8 to 5.9, respectively. The in vitro antiviral activity of these conjugates was determined and used to evaluate their potential applications in anti-AIDS drugs. The in vitro anti-HIV activities indicate that the synthesized polyrotaxane-AZT conjugates and their nanoparticles against HIV-1 and HIV-2 strains were more potent inhibitors than free AZT, with reduced cytotoxicities against uninfected MT-4 cells. The effect of the conjugates against HIV-1 and HIV-2 strains increased with decreasing particle size. (C) 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 50: 4895-4901, 2012