A new hyaluronan derivative modified with β-cyclodextrin units (CD-HA) was prepared via the click reaction between propargylated hyaluronan and monoazido-cyclodextrin (CD) to achieve a degree of substitution of 4%. The modified hyaluronan was characterized by 1H-nuclear magnetic resonance spectroscopy (NMR) and size exclusion chromatography. Subsequent 1H-NMR and isothermal calorimetric titration experiments revealed that the CD units on CD-HA can form virtual 1:1, 1:2, and 1:3 complexes with one-, two-, and three-site adamantane-based guests, respectively. These results imply that the CD-HA chains used the multitopic guests to form a supramolecular cross-linked network. The free CD-HA polymer was readily restored by the addition of a competing macrocycle, which entrapped the cross-linking guests. Thus, we demonstrated that the new CD-HA polymer is a promising component for the construction of chemical stimuli-responsive supramolecular architectures.

Centre of the Region Haná for Biotechnological and Agricultural Research Department of Chemical Biology and Genetics Faculty of Science Palacký University Olomouc Šlechtitelů 241 27 CZ 783 71 Olomouc Czech Republic

Department of Chemistry Faculty of Technology Tomas Bata University in Zlín Vavrečkova 275 760 01 Zlin Czech Republic

Department of Fat Surfactant and Cosmetics Technology Faculty of Technology Tomas Bata University in Zlín Vavrečkova 275 760 01 Zlin Czech Republic

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Rao M.G., Bharathi P., Akila R.M. A comprehensive review on biopolymers. Sci. Revs. Chem. Commun. 2014;4:61–68.

Bernkop-Schnurch A., Dunnhaupt S. Chitosan-based drug delivery systems. Eur. J. Pharm. Biopharm. 2012;81:463–469. doi: 10.1016/j.ejpb.2012.04.007. PubMed DOI

Jin Y.J., Ubonvan T., Kim D.D. Hyaluronic acid in drug delivery systems. J. Pharm. Invest. 2010;40:33–43. doi: 10.4333/KPS.2010.40.S.033. DOI

Huang G., Huang H. Application of hyaluronic acid as carriers in drug delivery. Drug Deliv. 2018;25:766–772. doi: 10.1080/10717544.2018.1450910. PubMed DOI PMC

Hirakura T., Yasugi K., Nemoto T. Hybrid hyaluronan hydrogel encapsulating nanogel as a protein nanocarrier new system for sustained delivery of protein with a chaperone-like function. J. Control. Release. 2010;142:483–489. doi: 10.1016/j.jconrel.2009.11.023. PubMed DOI

Zhang L.M., Wu C.X., Huang J.Y., Peng H.X., Chen P., Tang S.Q. Synthesis and characterization of a degradable composite agarose/HA hydrogel. Carbohydr. Polym. 2012;88:1445–1452. doi: 10.1016/j.carbpol.2012.02.050. DOI

Vercruysse K.P., Prestwich G.D. Hyaluronate derivatives in the drug delivery. Crit. Rev. Ther. Drug Carr. Syst. 1998;15:513–555. doi: 10.1615/CritRevTherDrugCarrierSyst.v15.i5.30. PubMed DOI

Schante C.E., Zuber G., Herlin C., Vandamme T.F. Chemical modifications of hyaluronic acid for the synthesis of derivatives for a broad range of biomedical applications. Carbohydr. Polym. 2011;85:469–489. doi: 10.1016/j.carbpol.2011.03.019. DOI

Zhang W., Mu H., Dong D., Wang D., Zhang A., Duan J. Alteration in immune responses toward N-deacetylation of hyaluronic acid. Glycobiology. 2014;24:1334–1342. doi: 10.1093/glycob/cwu079. PubMed DOI

Bulpitt P., Aeschlimann D. New strategy for chemical modification of hyaluronic acid: Preparation of functionalized derivatives and their use in the formation of novel biocompatible hydrogels. J. Biomed. Mater. Res. 1999;47:152–169. doi: 10.1002/(SICI)1097-4636(199911)47:2<152::AID-JBM5>3.0.CO;2-I. PubMed DOI

Crescenzi V., Francescangeli A., Segre A.L., Capitani D., Mannina L., Renier D., Bellini D. NMR structural study of hydrogels based on partially deacetylated hyaluronan. Macromol. Biosci. 2002;2:272–279. doi: 10.1002/1616-5195(200208)2:6<272::AID-MABI272>3.0.CO;2-V. DOI

Xu X., Jha A., Harrington D., Farach-Carson M., Jia X. Hyaluronic acid-based hydrogels from a natural polysaccharide to complex networks. Soft Matter. 2012;8:328–329. doi: 10.1039/c2sm06463d. PubMed DOI PMC

Highley C.B., Prestwich G.D., Burdick J.A. Recent advances in hyaluronic acid hydrogels for biomedical applications. Curr. Opin. Biotechnol. 2016;40:35–40. doi: 10.1016/j.copbio.2016.02.008. PubMed DOI

Segura T., Anderson B.C., Chung P.H., Webber R.E., Shull K.R., Shea L.D. Crosslinked hyaluronic acid hydrogels a strategy to functionalize and pattern. Biomaterials. 2005;26:359–371. doi: 10.1016/j.biomaterials.2004.02.067. PubMed DOI

Hahn S.K., Jelacic S., Maier R.V., Stayton P.S., Hoffman A.S. Anti-inflammatory drug delivery from hyaluronic acid hydrogels. J. Biomater. Sci. Polym. Ed. 2004;15:1111–1119. doi: 10.1163/1568562041753115. PubMed DOI

Tomihata K., Ikada Y. Cross-linking of hyaluronic acid with glutaraldehyde. J. Polym. Sci. Part A Polym. Chem. 1997;35:3553–3559. doi: 10.1002/(SICI)1099-0518(19971130)35:16<3553::AID-POLA22>3.0.CO;2-D. DOI

Kuo J.W., Swann D.A., Prestwich G.D. Chemical modification of hyaluronic acid by carbodiimides. Bioconjug. Chem. 1991;2:232–241. doi: 10.1021/bc00010a007. PubMed DOI

Ma X., Tian H. Stimuli-responsive supramolecular polymers in aqueous solution. Acc. Chem. Res. 2014;47:1971–1981. doi: 10.1021/ar500033n. PubMed DOI

Dong R., Zhou Y., Huang X., Zhu X., Lu Y., Shen J. Functional supramolecular polymers for biomedical applications. Adv. Mater. 2015;27:498–526. doi: 10.1002/adma.201402975. PubMed DOI

Harada A. Supramolecular polymers based on cyclodextrins. J. Polym. Sci. Part A Polym. Chem. 2006;44:5113–5119. doi: 10.1002/pola.21618. DOI

Rodell C.B., Kaminski A.L., Burdick J.A. Rational design of network properties in guest-host assembled and shear-thinning hyaluronic acid hydrogels. Biomacromolecules. 2013;14:4125–4134. doi: 10.1021/bm401280z. PubMed DOI PMC

Zhu L.L., Li X., Ji F.Y., Ma X., Wang Q.C., Tian H. Photolockable ratiometric viscosity sensitivity of cyclodextrin polypseudorotaxane with light-active rotor graft. Langmuir. 2009;25:3482–3486. doi: 10.1021/la8042457. PubMed DOI

Yang Y., Zhang Y.M., Chen Y., Chen J.T., Liu Y. Polysaccharide-based noncovalent assembly for targeted delivery of taxol. Sci. Rep. 2016;6:19212. doi: 10.1038/srep19212. PubMed DOI PMC

Zhang Y.H., Zhang Y.M., Yang Y., Chen L.X., Liu Y. Controlled DNA condensation and targeted cellular imaging by ligand exchange in a polysaccharide-quantum dot conjugate. Chem. Commun. 2016;52:6087–6090. doi: 10.1039/C6CC01571A. PubMed DOI

Kim S.H., In I., Park S.Y. pH-Responsive NIR-absorbing fluorescent polydopamine with hyaluronic acid for dual targeting and synergistic effects of photothermal and chemotherapy. Biomacromolecules. 2017;18:1825–1835. doi: 10.1021/acs.biomac.7b00267. PubMed DOI

Zhao Q., Chen Y., Sun M., Wu X.J., Liu Y. Construction and drug delivery of a fluorescent TPE-bridged cyclodextrin/hyaluronic acid supramolecular assembles. RSC Adv. 2016;6:50673–50679. doi: 10.1039/C6RA07572J. DOI

Badwaik V., Liu L., Gunasekera D., Kulkarni A., Thompson D.H. Mechanistic insight into receptor-mediated Delivery of Cationic-β-Cyclodextrin: Hyaluronic Acid-Adamantamethamidyl Host-Guest p-DNA nanoparticles to CD44+ Cells. Mol. Pharm. 2016;13:1176–1184. doi: 10.1021/acs.molpharmaceut.6b00078. PubMed DOI PMC

Piperno A., Zagami R., Cordaro A., Pennisi R., Musarra-Pizzo M., Scala A., Sciortino M.T., Mazzaglia A. Exploring the entrapment of antiviral agents in hyaluronic acid-cyclodextrin conjugates. J. Incl. Phenom. Macrocycl. Chem. 2019;93:33–40. doi: 10.1007/s10847-018-0829-6. DOI

Banerji S., Wright A.J., Noble M., Mahoney D.J., Campbell I.D., Day A.J., Jackson D.G. Structures of the Cd44-hyaluronan complex provide insight into a fundamental carbohydrate-protein interaction. Nat. Struct. Mol. Biol. 2007;14:234–239. doi: 10.1038/nsmb1201. PubMed DOI

Zhong S.P., Campoccia D., Doherty P.J., Williams R.L., Benedetti L., Williams D.F. Biodegradation of hyaluronic acid derivatives by hyaluronidase. Biomaterials. 1994;15:359–365. doi: 10.1016/0142-9612(94)90248-8. PubMed DOI

Raoov M., Mohamad S.H., Radzi M. Synthesis and characterization of β-cyclodextrin functionalized ionic liquid polymer as a macroporous material for the removal of phenols and As (V) Int. J. Mol. Sci. 2014;15:100–119. doi: 10.3390/ijms15010100. PubMed DOI PMC

Nielsen T.T., Wintgens V., Amiel C., Wimmer R., Lambertsen K. Facile synthesis of β-cyclodextrin-dextran polymers by click chemistry. Biomacromolecules. 2010;11:1710–1715. doi: 10.1021/bm9013233. PubMed DOI

Huerta-Angeles G., Němcova M., Přikopová E., Šmjekalová D., Pravda M., Kučera L., Velebný V. Reductive alkylation of hyaluronic acid for the synthesis of biocompatible hydrogels by click chemistry. Carbohydr. Polym. 2012;90:1704–1711. doi: 10.1016/j.carbpol.2012.07.054. PubMed DOI

Rekharsky M.V., Inoue Y. Complexation Thermodynamics of Cyclodextrins. Chem. Rev. 1998;98:1875–1918. doi: 10.1021/cr970015o. PubMed DOI

Moghaddam S., Yang C., Rekharsky M., Ko Y.H., Inoue Y., Gilson M.K. New Ultrahigh Affinity Host-Guest Complexes of Cucurbit[7]uril with Bicyclo[2.2.2]octane and Adamantane Guests: Thermodynamic Analysis and Evaluation of M2 Affinity Calculations. J. Am. Chem. Soc. 2011;133:3570–3581. doi: 10.1021/ja109904u. PubMed DOI PMC

Branná P., Rouchal M., Prucková Z., Dastychová L., Lenobel R., Pospíšil T., Maláč K., Vícha R. Rotaxanes capped with host molecules: Supramolecular behavior of adamantylated bisimidazolium salts containing a biphenyl centerpiece. Chem. Eur. J. 2015;21:11712–11718. PubMed

Kulkarni S.G., Prucková Z., Rouchal M., Dastychová L., Vícha R. Adamantylated trisimidazolium-based tritopic guests and their binding properties towards cucurbit[7]uril and β-cyclodextrin. J. Incl. Phenom. Macrocycl. Chem. 2016;84:11–20. doi: 10.1007/s10847-015-0577-9. DOI

Schneider H.-J., Hacket F., Rüdiger V., Ikeda H. NMR Studies of Cyclodextrins and Cyclodextrin Complexes. Chem. Rev. 1998;98:1755–1785. doi: 10.1021/cr970019t. PubMed DOI

Assaf K.I., Nau W.M. Cucurbiturils: From synthesis to high-affinity binding and catalysis. Chem. Soc. Rev. 2015;44:394–418. doi: 10.1039/C4CS00273C. PubMed DOI

Barrow S.J., Kasera S., Rowland M.J., del Barrio J., Scherman O.A. Cucurbituril-Based Molecular Recognition. Chem. Rev. 2015;115:12320–12406. doi: 10.1021/acs.chemrev.5b00341. PubMed DOI