Engineered Self-Assembly of Amphiphilic Cyclodextrin Conjugates for Drug Encapsulation.

Abstract

Cyclodextrins are a group of naturally occurring oligosaccharides that have widely been studied and applied in pharmaceutical formulations forming inclusion complexes with a broad variety of drugs exhibiting different hydrophilicity as well as molecular weights. Grafting aliphatic chains onto native cyclodextrins renders them amphiphilic and enables self-assembly into supramolecular structures that have already been explored for drug delivery. Based on the possibility of controlling the inherent physicochemical properties by modifying their chemical structure, amphiphilic cyclodextrin conjugates hold a great potential to become a drug delivery platform adaptable to the individual needs of specific active drug molecules. In this work, a library of amphiphilic cyclodextrin derivatives was synthesized by conjugating aliphatic chains of different lengths to native β-cyclodextrin via thioether or ester bonds. Upon nanoprecipitation, the synthesized amphiphilic cyclodextrin derivatives spontaneously self-assembled into nanosized supramolecular structures with a monodisperse size distribution. We systematically investigated the relationship between the molecular structure of the amphiphilic cyclodextrin derivatives and the corresponding self-assembly into nanosystems as well as the encapsulation of model drugs with different physicochemical properties. Encapsulation efficiencies up to 97% and pH-dependent release profiles were achieved. We found that both the aliphatic chain length and the linker molecule determine the respective self-assembly and drug encapsulation mechanism of the individual system. The colloidal stability and biocompatibility with human cells of all derivatives were proven. Consequently, amphiphilic cyclodextrin conjugates provide a drug delivery platform with tailor-made control over physicochemical properties and high drug encapsulation efficiency for a broad range of drug molecules, thus offering great potential for the development of future therapeutics with improved therapeutic efficiency.