Mobility of Water and Polymer Species and Rheological Properties of Supramolecular Polypseudorotaxane Gels Suitable for Bone Regeneration

Abstract

The aim of this work was to prepare polypseudorotaxane-based supramolecular gels combining αCD with two temperature-responsive copolymers of different architecture (i.e., linear poloxamer P and X-shaped poloxamine T), at the lowest concentration as possible to form syringeable depots, and to shed light on the self-diffusion and spatial closeness of all components (including water) which in turn may determine the cooperative self-assembly phenomena and the performance of the gels at the macroscopic level. The exchange rate between bound water and bulk water was measured with a novel NMR experiment Water Diffusion Exchange-Diffusion Optimized Spectroscopy (WDE-DOSY). Polypseudorotaxane formation caused opposite effects on the mobility of αCD species (decreased) and internal water (increased) but did not affect PPO-water interaction. Consequently, designed ternary P/T/αCD supramolecular gels exhibited in situ gelling at body temperature could host large amounts of PLA/PLGA microspheres and behaved as porous 3D-scaffolds for mesenchymal stem cells (MSCs) supporting their osteogenic differentiation. Interestingly, the gels withstood freeze-drying and reconstitution with minor changes in inner structure and rheological properties. The gathered information may help to understand better the supramolecular gels and provide tools for the rational design of syringeable bone scaffolds that can simultaneously accommodate cells and drug microcarriers for efficient tissue regeneration.

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

“…The visualization of two phases in the PF127/αCD 7% system suggested that the polypseudorotaxanes were somehow collapsed and could not form a complete 3D supramolecular gel filling the whole volume of the dispersion. This phase separation was not observed in previous reports on PF127/αCD polypseudorotaxanes prepared in pure water [37][38][39][40] and may be caused by an enhanced aggregation of the αCDs in the buffer pH 4.9 used to prepare the formulations. This acid pH adversely affects the solubility of the αCDs but is preferable for topical skin formulations.…”

“…Dt offers information about the molecular organization as it depends on the molecule size that can be calculated from the Stokes-Einstein equation. This value was slightly higher than that previously reported for related block copolymers [40]. In the presence of both cyclodextrins, the chemical environment surrounding these groups changed, confirming that the inclusion phenomenon took place.…”

“…The dispersions were prepared in citrate buffer (Table 1), dried and redispersed in D 2 O. We have previously observed that the drying step does not significantly modify the NMR results in this kind of systems [40]. The use of D 2 O instead of H 2 O:D 2 O mixtures may lead to faster polypseudorotaxane formation kinetics, but the final architecture of the polypseudorotaxanes is expected to be almost the same [43].…”

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

“…Interestingly, the presence of natamycin only caused a minor decrease in both G′ and G″, which means that Pluronic P103 attenuated the effects of hosting natamycin in Soluplus cores probably because of a preferential interaction of αCD molecules with the PEO blocks of Pluronic P103. It has been previously observed by means of nuclear magnetic resonance diffusion studies that the threading of αCD along PEO moieties of Pluronic F127 causes a remarkable decrease in αCD mobility [43], which is typical of strong complex formation. The decrease in the mobility of αCDs due to the formation of a transient complex with Soluplus was less marked [35], which supports our hypothesis of a preferential threading of αCDs along Pluronic P103 in the mixed micelles.…”

New injectable two-step forming hydrogel for delivery of bioactive substances in tissue regeneration

“…Moreover, the addition of cyclodextrins, a cyclic oligosaccharide composed of six to eight glucopyranose units, can lead to the formation of inclusion complexes with certain polymer regions. The toxicity of these compounds decreases with increasing number of glucopyranose units, thus, gamma cyclodextrins are less toxic than alpha or beta ones [11]. Synthetic polymers, like poly( dl -lactide-co-glycolide) (PLGA), poly( dl -lactide) (PLA), poly(vinyl alcohol) (PVA), poly(acrylic acid) (PAA), polyethylene glycol (PEG), can enhance and control the mechanical strength and degradation rates of hydrogels.…”