New application of a versatile drug nanocarrier based on a choline-calix[4]arene derivative: Supramolecular nanohydrogel formation in the presence of curcumin

The development of nano-structured systems able to deliver drugs to the biological targets are of great interest in biomedical field. In this context, we designed a supramolecular nanoaggregate of a polycationic choline-calix[4]arene derivative (1) to deliver drugs towards protected biological compartments (eye and brain) exposing choline-transporters. We demonstrated the potential of the micellar nanoconstruct as nanocarrier for natural and synthetic drugs, [1,2] and as nanoreactor for photoactivatable drugs. [3] The micellar nanoaggregates formed by simple dissolution in PBS medium, significantly increased water-solubility and stability of curcumin. [1,2] Interestedly, at higher concentrations the calix[4]arene 1 and curcumin formed a clear reddish hydrogel (Figure 1), rather than a colloidal solution. Herein, we report about the preparation, physico-chemical characterization and sustained drug release property of the supramolecular micellar nanohydrogel. Rheological properties, morphology, simulation modelling, protection of curcumin from photodegradation, and low rate of curcumin release upon to dissolution of the hydrogel in drug loaded micellar nanoaggregates, will be discussed. The visco-elastic and injectable supramolecolar nanohydrogel formed by simply addition of a natural drug like curcumin to a self-assembling calix[4]arene derivative, without using other additives and organic solvents, combines the properties of micellar systems and a hydrogel in drug delivery and appears a promising new tool for applications in nanomedicine.