Monodisperse Nanoparticles from Self-Assembling Amphiphilic Cyclodextrins: Modulable Tools for the Encapsulation and Controlled Release of Pharmaceuticals

Abstract

Selective chemical functionalization of cyclodextrins (CDs) is a readily amenable methodology to produce amphiphilic macromolecules endowed with modulable self-organizing capabilities. Herein, the synthesis of well-defined amphiphilic CD derivatives, with a "skirt-type" architecture, that incorporate long-chain fatty esters at the secondary hydroxyl rim and a variety of chemical functionalities (e. g. iodo, bromo, azido, cysteaminyl or isothiocyanato) at the primary hydroxyls rim is reported. Nanoprecipitation of the new CD facial amphiphiles, or binary mixtures of them, resulted in nanoparticles with average hydrodynamic diameters ranging from 100 to 240 nm that were stable in suspension for several months. The precise size, zeta potential and topology of the nanoparticles are intimately dependent on the functionalization pattern at the CD scaffold. Highly efficient molecular encapsulation capabilities of poorly bioavailable drugs such as diazepam (DZ) were demonstrated for certain derivatives, the drug release profile being dependent on the type of formulation (nanospheres or nanocapsules). The efficiency and versatility of the synthetic strategy, together with the possibility of exploiting the reactivity of the functional groups at the nanoparticle surface, offer excellent opportunities to further manipulate the carrier capabilities of this series of amphiphilic CDs from a bottom-up approach.