Tunable supramolecular self-assemblies based on cyclodextrin polymer as a loading platform for water-soluble drugs

Abstract

Drug loading capacity is a crucial character of nano-scaled drug carriers to achieve high quality pharmaceutical preparations. However, efficient encapsulation of water-soluble small molecular drugs still faces large obstacles in many cases. Herein, we designed a novel supramolecular delivery system constructed by poly(β-cyclodextrin) containing benzoic acid groups (PCD-PA) and adamantyl terminated poly(ethylene glycol) (PEG-AD) to provide multiple intermolecular interactions for competent loading of water-soluble small-molecular drugs. PCD-PA had multiple host molecules, and PEG-AD could be inserted via host-guest interaction in different proportion to adjust the composition of supramolecular carrier. Meanwhile, π-π stacking and electrostatic interaction furnished by benzoic acid groups served as binding force for drug entrapment, which led to considerable loading capacity for several water-soluble drugs. Among the drugs with different chemical structures, mitoxantrone hydrochloride and doxorubicin hydrochloride bearing anthraquinone rings and several protonable amino groups acquired the highest loading content as about 14 % in PCD-PA3/PEG-AD supramolecular self-assemblies. Further computational simulations investigated the mechanism of drug loading based on the interactions between the carrier materials and the payloads. In addition, the weakly acidic environment obviously accelerated the release of certain drugs. All in all, this self-assembled supramolecular nano-system displayed great potentials as a delivery platform for diverse water-soluble drugs.