hydrogels of hyaluronic acid functionalized with ：透明质酸官能水凝胶

,Preparation of Methacryloyl- b-Cyclodextrin Monomer for Hydrogel Functionalization,Scott A. Zawko1, Christine E. Schmidt1,2,1Department of Chemical Engineering2Department of Biomedical EngineeringThe University of Texas at Austin, Austin, TX,Composite Hydrogel Material,Large molecular weightHigh water contentHigh porosityBiocompatibleBiodegradable,Hyaluronic Acid,n,7,MW = 5x105 2x106,Goal: Create a hyaluronic acid hydrogel that binds and retains small molecules,Strategy:,Design a cyclodextrin monomer that binds and retains small molecules,Strategy:,g-cyclodextrin (n=8)b-cyclodextrin (n=7)a-cyclodextrin (n=6),Design a monomer that binds and retains small molecules,Hydrophilic Exterior,Hydrophobic Interior,Inclusion Complexes,+,Hydrocortisone,Marketed Drug-Cyclodextrin Complexes,Adapted from Davis M.E. and Brewster M.E. (2004) Nat Rev Drug Discov,Composite Hydrogel:,+,UV Light,I 2959,Hyaluronic acid functionalized with MAbCD,+,TEA,GMHA,GMHA Synthesis,Leach, J.B. et al. (2003) Biotechnol Bioeng,3500,Synthesis of Methacryloyl-b-Cyclodextrin,Possible steric hindrance,MAbCD4,Characterization: MALDI-TOF mass spectrometry,*,*,*,bCD,MAbCD,Characterization: 1H NMR (solvent: D2O),RP-HPLC Purification,Water:ACN gradient 98:2 to 45:55 0.8 mL/min,1,2,MAbCD,Impurities,Crude MAbCD,bCD,Characterization: 1H NMR (solvent: D2O),R = H or,Characterization: MALDI-TOF mass spectrometry,MAbCD: 1400 M-1,bCD: 5380 M-1,0,Quantitation of MAbCD-Hydrocortisone Binding,Fractionation of MAbCD,DS Dependent Solubility,p 0.05,Hyaluronic acid functionalized with MAbCD,Composite Hydrogel:,+,Phenolphthalein,GMHA-MAbCD Hydrogels: Hydrocortisone Loading,1 HC : 4.6 MAbCD,Gel20 mg/mL GMHA + 0, 0.5, 1.0 or 1.5 mg/mL MAbCD,Conclusions,Hyaluronic Acid,Cyclodextrin,n,MW = 5x105 2x106,CompositeGMHA-MAbCD,Photocrosslinked GelInclusion complexesLoaded with Hydrocortisone,AcknowledgementsDr. Klaus Linse Institute for Cellular and Molecular Biology, UT AustinSteve Sorey Nuclear Magnetic Resonance Laboratory, UT AustinCurt Deister, Nathalie Guimard, Quan Truong Sch