Degradable polycaprolactone nanoparticles stabilized via supramolecular host–guest interactions with pH-responsive polymer-pillar[5]arene conjugates

Smart nano-carriers such as micelles, vesicles or nanoparticles constructed from amphiphilic polymers promise a new generation of drug delivery systems featuring localized and controlled release. Keeping the considerable effort for the synthesis of these polymers in mind, supramolecular host–guest interactions represent an interesting alternative to engineer amphiphilic materials with multiple functionalities. Using the known interaction of pillar[5]arenes with aromatic guests such as viologen-derivatives, we designed quasi-block copolymers based on polycaprolactone (PCL) and either the neutral and biocompatible poly(N-acryloyl morpholine) (PNAM-P[5]) or the structurally similar but pH-responsive poly(N-acryloyl-N′-methyl piperazine) (PNAMP-P[5]), which were modified with the pillar[5]arene. Self-assembly experiments in water resulted in the formation of small spherical nanostructures for the methyl viologen-polycaprolactone (viologen-PCL), but surprisingly also for the non-functionalized PCL. However, only the pH-responsive PNAMP-P[5] provided stable structures in the buffer for both cases, while PNAM-P[5] resulted in aggregation. Additional degradation studies revealed that the presence of host–guest complexes could retard the disintegration of the particles at low pH (5.1) in comparison to the particles based on plain PCL, while all structures remained stable at neutral pH value. In combination with their excellent biocompatibility, the presented supramolecular approach to stabilize PCL nanoparticles with pH-responsive polymers pave a convenient way to degradable delivery systems with tailored release profiles.