Pseudo-Polyrotaxanes of Cyclodextrins with Direct and Reverse X-Shaped Block Copolymers: A Kinetic and Structural Study

Abstract

Pseudo-polyrotaxanes (PPRs) are supramolecular host-guest complexes constituted by the reversible threading of a macrocycle along a polymer chain, which offers potential applications in nanotechnology, drug delivery and biomaterials. We report the threading of cyclodextrins (CDs), cyclic oligosaccharides, onto X-shaped PEO-PPO block-copolymers, with two opposite presentation of their hydrophobic and hydrophilic blocks: Tetronic 904 (T904), and its reverse counterpart, Tetronic T90R4. We assess the effect of relative block position on the polymeric surfactants and cavity size of CD have on the composition, morphology, thermodynamics and kinetics of PPRs by using a combination of X-ray diffraction, Scanning Electron Microscopy (SEM), NMR, UV-Vis spectroscopy and Time-Resolved Small-Angle Neutron Scattering (TR-SANS). Solid PPRs with lamellar microstructure and crystalline channel-like structures are obtained with native CDs and both Tetronics above a threshold concentration of the macrocycle, which varies with the type of CD and surfactant. While γ-CD can form PPRs with both Tetronics, α-CD only form a PPR with T90R4 at high concentrations. The results can be explained in terms of the preferential complexation of α-CD with EO and γ-CD with PO monomers, which also has a direct impact on the kinetics of PPR formation. Thermodynamic parameters of the reaction were obtained from the analysis of the stoichiometries and threading times as a function of temperature by using a model based on the Eyring equation. Negative enthalpies and positive entropies are obtained in all cases, and reactions are thermodynamically most favorable in the case of α-CD with T904 and γ-CD with T90R4. TR-SANS experiments reveal an increase in the radius of gyration of the unimers over time, consistent with CDthreading and expansion of the PPR. Above the CMT, α-CD threads the unimers to form the PPR, with no effect on the structure of T904 micelles, whose volume fraction decreases due to the shift of micellization equilibrium.

Polypseudorotaxanes of Pluronic® F127 with Combinations of α- and β-Cyclodextrins for Topical Formulation of Acyclovir

“…The characteristic peaks of PF127 ( Figure 2A) appeared at diffraction angles of 19.19 and 23.31 • 2 θ [37]. In presence of high concentrations of αCD (i.e., 7% αCD and αCD 6%/βCD 1%) the formulation showed well defined peaks at 12.9 • and 19.9 • , which are characteristic of a channel type crystalline structure with αCD units organized head-to-head and tail-to-tail, typical for polypseudorotaxanes [38,39,42]. The intensity of these peaks decreased as the βCD relative concentration increased.…”

“…Both molar ratios were well above the 2:1 stoichiometry reported for EO:αCD and PO:βCD complex formation [22,41], which means that there are CD-free regions in the copolymer chains. Therefore, the designed supramolecular gels may be formed by a mixture of polymeric nanomicelles and aggregates of nanosized polypseudorotaxanes that assemble forming interconnected macrostructures [22,41,42].…”

Cyclodextrin–Amphiphilic Copolymer Supramolecular Assemblies for the Ocular Delivery of Natamycin

“…The combination of amphiphilic copolymers and cyclodextrins has also been shown to prolong drug permeation at the application site [28,35]. In particular, α-cyclodextrin (αCD) can thread on some block polymers, for example, PEO, and reinforce the hydrophobic interactions among the components through crystalline-like associations among the threaded CDs [36] notably increasing the viscoelastic properties of the system. Such reinforcement is reversible, and thus, under a small amount of pressure, the interactions between αCD molecules are broken, increasing the fluidity of the system.…”

Threading Different Rings on X-Shaped Block Copolymers: Hybrid Pseudopolyrotaxanes of Cyclodextrins and Tetronics

“…In the case of poloxamines, the higher affinity of α-CD towards EO monomers leads to a preferential localization of the macrocycle on the outer PEO blocks, followed by precipitation of the PPR if the concentration of native CD is high enough. 33 Instead, DIMEB is expected to thread preferentially on the PPO blocks to produce a water-soluble PPR. 32 When both macrocycles are combined, the result is the formation of a "hybrid" PPR (hPPR).…”