Hydrophobic pharmaceuticals mediated self-assembly of beta-cyclodextrin containing hydrophilic copolymers: novel chemical responsive nano-vehicles for drug delivery.

Double hydrophilic copolymers with one polyethylene glycol (PEG) block and one beta-cyclodextrin (beta-CD) flanking block (PEG-b-PCDs) were synthesized through the post-modification of macromolecules. The self-assembly of PEG-b-PCDs in aqueous solutions was initially studied by a fluorescence technique. This measurement together with AFM and TEM characterizations demonstrated the formation of nanoparticles in the presence of lipophilic small molecules. The host-guest interaction between the beta-CD unit of a host copolymer and the hydrophobic group of a guest molecule was found to be the driving force for the observed self-assembly. This spontaneous assembly upon loading of guest molecules was also observed for hydrophobic drugs with various chemical structures. Relatively high drug loading was achieved by this approach. Desirable encapsulation was also achieved for the hydrophobic drugs that cannot efficiently interact with free beta-CD. In vitro release studies suggested that the payload in nano-assemblies could be released in a sustained manner. In addition, both the fluorescence measurement and the in vitro drug release studies suggested that these nano-assemblies mediated by the inclusion complexation exhibited a chemical sensitivity. The release of payload can be accelerated upon the triggering by hydrophobic guest molecules or free beta-CD molecules. These results support the potential applications of the synthesized copolymers for the delivery of hydrophobic drugs.