Injectable supramolecular hydrogels based on custom-made poly(ether urethane)s and α-cyclodextrins as efficient delivery vehicles of curcumin.

Alessandro Torchio, Claudio Cassino, Mario Lavella, Andrea Gallina, Alice Stefani, Monica Boffito, Gianluca Ciardelli

Materials science & engineering. C, Materials for biological applications 2021 Aug

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A strategy to enhance drug effectiveness while minimizing controversial effects consists in exploiting host-guest interactions. Moreover, these phenomena can induce the self-assembly of physical hydrogels as effective tools to treat various pathologies (e.g., chronic wounds or cancer). Here, two Poloxamers®/Pluronics® (P407/F127 and P188/F68) were utilized to synthesize various LEGO-like poly(ether urethane)s (PEUs) to develop a library of tunable and injectable supramolecular hydrogels for drug delivery. Three PEUs were synthesized by chain extending Poloxamer/Pluronic with 1,6-cyclohexanedimethanol or N-Boc serinol. Other two amino-functionalized and highly responsive polymers were obtained thorough Boc-group cleavage. For hydrogel design, the spontaneous self-assembly of the poly(ethylene oxide) domains of PEUs with α-cyclodextrins was exploited to form poly(pseudo)rotaxanes (PPRs). PPR-derived channel-like crystals were characterized by X-Ray powder diffraction, Infra-Red and Proton Nuclear Magnetic Resonance spectroscopies. Cytocompatible hydrogel formulations were designed at PEU concentrations between 1% and 5% w/v and α-cyclodextrin at 10% w/v. Supramolecular gels showed good mechanical performances (storage modulus up to 20 kPa) coupled with marked thixotropic and self-healing properties (mechanical recovery over 80% within 30 s after cyclic rupture) as assessed through rheology. Hydrogels exhibited stability and high responsiveness in watery environment up to 5 days: the release of less stable components as suitable drug carriers was coupled with high swelling (doubling the content of fluids with respect to their dry mass) and shape retention. Curcumin was encapsulated into the hydrogels at high concentration (80 μg ml-1) through its complexation with α-cyclodextrins and delivery tests showed controllable and progressive release profiles up to four days. Copyright © 2021 Elsevier B.V. All rights reserved.

Citation

Alessandro Torchio, Claudio Cassino, Mario Lavella, Andrea Gallina, Alice Stefani, Monica Boffito, Gianluca Ciardelli. Injectable supramolecular hydrogels based on custom-made poly(ether urethane)s and α-cyclodextrins as efficient delivery vehicles of curcumin. Materials science & engineering. C, Materials for biological applications. 2021 Aug;127:112194