Experimental and theoretical studies of pegylated-β-cyclodextrin: A step forward to understand its tunable self-aggregation abilities

In this work we studied the self-aggregation abilities of βCDPEG5, a star-shaped pegylated derivative comprising seven PEG chains selectively conjugated to the primary face of βCD via triazole linkers. The critical aggregation concentration, determined by density measurements, yielded a value of 0.5 mM. Dynamic light scattering (DLS) showed that βCDPEG5 forms nanoaggregates of a hydrodynamic diameter (Dh) of ∼150 nm in water at 25 °C. βCDPEG5 significantly decreased the surface tension of water, thus confirming the aggregation phenomenon. Transmission electron microscopy upheld the presence of the nanoaggregates and revealed their quasi-spherical shape. Nanostructures of 9 nm coexisting with the nanoaggregates were also observed in DLS and correspond to βCDPEG5 dimers. Computational studies analyzed dimers as the initial stage in the βCDPEG5 nanoaggregation process. Both βCDPEG5 nanoaggregates and dimers displayed their same Dh pattern in acidic, neutral, and basic conditions; likewise, when modifying the ionic strength of the medium. Interestingly, the nanoaggregates and dimers varied depending on the experimental conditions, being the former predominant when increasing pH and ionic strength, a behavior attributed to the triazole linkers, which seem to respond smartly to changes in the environment. At 37 °C, only βCDPEG5 nanoaggregates were present with a Dh mean value similar to that at 25 °C. The scattering behavior of nanoaggregates and dimers was studied for 55 days. We found that Dh of both species remains unchanged; nevertheless, at the end of the analysis, the nanoaggregates population was predominant. These overall results demonstrate that βCDPEG5 is an amphiphilic non-ionic system with a remarkable ability to aggregate in water and form defined nanostructures. Moreover, depending on the βCDPEG5 concentration, pH, ionic strength, and temperature, the dimeric or nanoaggregated state can be tuned, being this an attractive feature to load and control the release of a drug. [Display omitted] •Self-aggregation of a pegylated βCD derivative is investigated through several techniques.•Critical Aggregation Concentration for Pegylated βCD was 0.5 mM.•Pegylated-βCD forms nanoaggregates and dimers of ∼150 nm and 9 nm respectively.•Temperature, pH, ionic strength and concentration influence nanoaggregates and dimers formation.•Tunning dimeric or aggregate state: advantageous to control drug loading and release.