Supramolecular Hybrid Structures and Gels from Host–Guest Interactions between α-Cyclodextrin and PEGylated Organosilica Nanoparticles

Abstract

Polypseudorotaxanes are polymer chains threaded by molecular rings that are free to unthread; these "pearl-necklace" can self-assemble further, leading to higher-order supramolecular structures with interesting functionalities. In this work, the complexation between α-cyclodextrin (α-CD), a cyclic oligosaccharide of glucopyranose units, and poly(ethylene glycol) (PEG) grafted to silica nanoparticles was studied. The threading of α-CD onto the polymeric chains leads to their aggregation into bundles, followed by either the precipitation of the inclusion complex or the formation of a gel phase, in which silica nanoparticles are incorporated. The kinetics of threading, followed by turbidimetry, revealed a dependence of the rate of complexation on the following parameters: the concentration of α-CD, temperature, PEG length (750, 4000, and 5000 g mol), whether the polymer is grafted or free in solution, and the density of grafting. Complexation is slower, and temperature has a higher impact on PEG grafted on silica nanoparticles compared to PEG free in solution. Thermodynamic parameters extracted from the transition-state theory showed that inclusion complex formation is favored with grafted PEG compared to free PEG and establishes a ratio of complexation of five to six ethylene oxide units per cyclodextrin. The complexation yields, determined by gravimetry, revealed that much higher yields are obtained with longer chains and higher grafting density. Thermogravimetric analysis and Fourier transform infrared spectroscopy on the inclusion complex corroborate the number of macrocycles threaded on the chains. A sol-gel transition was observed with the longer PEG chain (5k) at specific mixing ratios; oscillatory shear rheology measurements confirmed a highly solid-like behavior, with an elastic modulus G' of up to 25 kPa, higher than that in the absence of silica. These results thus provide the key parameters dictating inclusion complex formation between cyclodextrin and PEG covalently attached to colloidal silica and demonstrate a facile route toward soft nanoparticle gels based on host-guest interactions.

Hydrogel design strategies for drug delivery

“…CPs are versatile materials that are attracting increasing interest in particular for bioimaging applications (63)(64)(65). Liu et al for instance exploited the well-known host-guest interaction between PEG and -cyclodextrin to build hydrogels (66), where PEG chains were grafted on a CP backbone (poly(N-phenylglycine, PNPG), endowing the gel with high photothermal conversion efficiency (=52.6%) (54) (Figure 2B), which allowed the triggered release of DOX. The host-guest complexes acting as cross-links to the network impart shear-thinning properties and thus injectability.…”

Reinforced Supramolecular Hydrogels from Attapulgite and Cyclodextrin Pseudopolyrotaxane for Sustained Intra‐Articular Drug Delivery

“…Similar with other hybrid PPR systems, the strong hydrogen bond interactions among adjacent PPRs can provide the socalled supra-cross-links, in which the ATP served as a constant cross-linker to promote the formation of hybrid hydrogel together (Figure 2a). [15][16][17][18][19][20][21][22][23][24][25][38][39][40] Complementary X-ray diffraction (XRD) studies of freeze-dried hybrid hydrogels and native PPR hydrogel (PEG 5000 /α-CDs) were performed to further confirm the PPR formation in hybrid hydrogels. As shown in Figure 2c, the hybrid hydrogels all show the same pattern with native PPR hydrogel (G1), in which a typical diffraction peak at 2θ = 19.8°-20.0° could be clearly observed, attributed to the rigid crystalline structure of PEG and α-CD complex.…”

“…Among them, the pseudopolyrotaxane (PPR) hydrogel, fabricated based on the supramolecular host–guest interactions between poly(ethylene glycol) (PEG) and α‐cyclodextrins (α‐CDs), is promising as a carrier for IA drug delivery due to its good syringeability, biodegradability, nontoxicity, and nonimmunogenicity. [ 15–22 ] However, the native PPR hydrogels usually suffer from mechanical weakness, which greatly limits their further application. Studies on constructing hybrid supramolecular hydrogels in our previous work and other research groups have proved that the mechanical properties of hydrogels can be significantly improved through introducing 2D or 3D rigid inorganic particles as reinforcers, such as SiO 2 /organosilica nanoparticles, gold nanoparticles, graphene oxide, graphitic carbon nitride (g‐CN), and clay nanoplatelet.…”

“…Studies on constructing hybrid supramolecular hydrogels in our previous work and other research groups have proved that the mechanical properties of hydrogels can be significantly improved through introducing 2D or 3D rigid inorganic particles as reinforcers, such as SiO 2 /organosilica nanoparticles, gold nanoparticles, graphene oxide, graphitic carbon nitride (g‐CN), and clay nanoplatelet. [ 21–29 ] In these systems, the 3D network of supramolecular hydrogels will be strengthened taking advantage of the multidimensional characteristics of the reinforcing agent, and these reinforcing agents almost have no effect on the unique shear‐thinning and thixotropy properties, but effectively enhance the mechanical properties of the hybrid PPR hydrogel. Inspired by the phenomenon of “reinforced concrete,” we further consider that the introduction of a 1D, rigid, and rod‐like nanomaterial may play a role similar to the “reinforcement in concrete” and also improve the mechanical property of the PPR hydrogels.…”

Responsive Polypseudorotaxane Hydrogels Triggered by a Compatible Stimulus of CO2

“…The strength and the gelation concentration of the supramolecular hydrogels are highly dependent on the intermolecular hydrophobic interactions of the blocks copolymer. In branched systems, the guest moieties are various PEG‐grafted polymers, such as PEGylated organosilica nanoparticles, PEG modified gold nanocrystals …”