This study presents the construction and evaluation of highly efficient nanomedicines via self-assembly directed by multiple non-covalent interactions between carrier polymer and cargo molecules, including hydrophobic, host-guest recognition, hydrogen bonding and electrostatic forces. β-Cyclodextrin conjugated polyethyleneimine (PEI-CD) was employed as the model carrier material, while indomethacin (IND), a nonsteroidal anti-inflammatory drug, was used as the drug model. Spontaneous assembly of PEI-CD and IND led to core-shell structured nanoparticles with a positive surface and pH-triggering behavior as well as high drug loading capacity. These nano-assemblies can function as gastro-OFF/intestinal-ON delivery systems to selectively transport payload to enteric sites, thereby dramatically increasing the oral bioavailability of the loaded therapeutic, which can also serve as multifunctional nano-platforms for multiple delivery of various therapeutics. In addition, the strategy employed herein may provide new insights into the design of novel nanocarriers by self-assembling.
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