Preparation And Biomedical Application Of HA Based Supramolecular Hydrogel And Nanogel

Hyaluronic acid (HA), a member belongs to glycosaminoglycan (GAG) family, is themain components of the extracellular matrix and has been widely used for biomedicalapplication due to its good biological compatibility and special physiological properties. Astissue engineering scaffold material, hyaluronic acid can fully simulate the mechanical andchemical properties of tissues and improve the biocompatibility and viscoelasticity ofhydrogel. As a drug carrier, hyaluronic acid can enhance therapeutic effect and reduce the sideeffects of drugs. On the basis of numerous previous research works, we designedsupramolecular hydrogel as cell scaffold for tissue engineering and nanogel as drug carrier intumor target therapy research.(1) Hyaluronic acid-dextran supramolecular hydrogelIn situ forming hydrogels were prepared through supramolecular assembly of hyaluronicacid-β-cyclodextrin conjugate (HA-CD) and dextran-2-naphthylacetic acid conjugate(Dex-NAA). The chemical structures of two gelators (HA-CD and Dex-NAA) werecharacterized and confirmed by1H NMR spectra. The degree of substitution (DS) of HA-CDand Dex-NAA was determined to be0.16and0.07respectively. The concentration of HA-CDwas fixed at10wt%through pre-experiment, the mixing solution of HA-CD and Dex-NAAcould form gel at room temperature in less than30s with the concentration of Dex-NAA from10to30%. Scanning electron microscopy (SEM) confirmed its neatly and orderly porousstructure, pore size range of10~50μm; Rheological tests confirmed that the value of storagemodulus is higher than loss modulus, which was characteristic rheological behaviors of solidlike gel material. Moreover, their pore size, gelation time, swelling ratio as well as moduluscould be adjusted by altering the compositions between HA-CD and Dex-NAA. NIH/3T3cells entrapped in HA-Dex hydrogel showed favorable viability with the cell survival rate of91.48%. The results above demonstrated that the supramolecular assembled HA-Dexhydrogels could be promising to use as cell scaffold for tissue engineering.(2) Hyaluronic acid-pluronic nanogelHyaluronic acid-pluronic-F-127(HP) conjugate was designed and prepared via “Click”chemistry for targeted drug delivery. The resulting amphiphile was able to self-assemble intonanosized gel under hydrophobic forces. The chemical structure of HP conjugate wascharacterized and confirmed by1H NMR spectra and the degree of substitution (DS) wasdetermined to be0.13. Dynamic light scattering (DLS) and transmission electron microscope(TEM) results confirmed its temperature sensitivity. Within the range of temperature studied,particle size decreased from275.5nm to28.1nm, VPTT was determined to be25.5oC. When the concentration was above CGC, viscosity increased and the macro gel formed. HP nanogelof this concentration showed reversible sol-gel transition behavior and CGC was determinedto be23%. Doxorubicin (DOX) was loaded into HP nanogel as model hydrophobic drug, andthe behavior of good loading capacity and sustained release was observed. Cytotoxicity assayconfirmed that DOX-loaded micelles could efficiently internalize into HeLa cells and showsignificant distinction of IC50between tumor cells and normal cells. In vitro cellular uptakeassay confirmed effective cellular uptaking of receptor mediated endocytosis. Taken together,HP nanogel may be promising in drug delivery.