Design, synthesis, and in vitro evaluation of new amphiphilic cyclodextrin-based nanoparticles for the incorporation and controlled release of acyclovir

Acyclovir possesses low solubility in water and in lipid bilayers, so that its dosage forms do not allow suitable drug levels at target sites following oral, local, or parenteral administration. In order to improve this lack of solubility, new cyclodextrin-based amphiphilic derivatives have been designed to form nanoparticles, allowing the efficient encapsulation of this hydrophobic antiviral agent. The present work first describes the synthesis and characterization of five new O-2,O-3 permethylated O-6 alkylthio- and perfluoroalkyl-propanethio-amphiphilic beta-cyclodextrins. These derivatives have been obtained with good overall yields. The capacity of these molecules to form nanoparticles in water and to encapsulate acyclovir has then been studied. The nanoparticles prepared from the new beta-cyclodextrin derivatives have been characterized by dynamic light scattering and have an average size of 120 nm for the fluorinated derivatives and 220 nm for the hydrogenated analogs. They all allowed high loading and sustained release of acyclovir. (c) 2012 Elsevier B.V. All rights reserved.