Novel nanoparticles made from amphiphilic perfluoroalkyl α-cyclodextrin derivatives: Preparation, characterization and application to the transport of acyclovir

Abstract

The preparation of aqueous suspensions of nanoparticles of the fluorinated amphiphilic α-cyclodextrins hexakis[6-deoxy-6-(3-perfluoroalkylpropanethio)-2,3-di- O-methyl]-α-cyclodextrin and their hydrocarbon analogues was studied. The complexation of acyclovir by modified α-cyclodextrin, the encapsulation efficiency and release profile were measured as an assessment of the properties of such nanoparticles regarding drug delivery applications. Stable aqueous suspensions of nanoparticles were prepared using nanoprecipitation method without using surface-active agent. The organic solvent (ethanol) and cyclodextrin concentration (0.4 mM) were carefully selected. The nanoparticles prepared from these new amphiphilic α-cyclodextrin derivatives according to optimized conditions have an average diameter of 100 nm for fluorinated derivatives and 150 nm for hydrocarbon analogues. Suspensions were stable over at least 9 months. Acyclovir forms inclusion complexes of 1:1 stoichiometry and high stability constants (from 700 mol L −1 to 4000 mol L −1 in ethanol) as assessed from UV/vis spectroscopy and Electrospray Ionization Mass Spectroscopy. Satisfactory loading of acyclovir inside the nanoparticles was achieved according to the “highly loaded” preparation method (encapsulation efficiency ≈ 40%). Nanoparticles based on the fluorinated compounds delayed the drug release up to 3 h with little initial burst release. Fluorinated amphiphilic α-cyclodextrins self-assemble in the form of nanospheres that encapsulate acyclovir and allow sustained release, showing their potential for applications to drug delivery.