Multiresponsive hyaluronan-p(NiPAAm) "click"-linked hydrogels.
Combined reversible addition-fragmentation chain transfer (RAFT) and chemoselective "click" chemistry are used for assembling two polymeric chains into a hybrid network capable to respond simultaneously or separately to different external stimuli. An azido-derivative of hyaluronate is clicked together with a new telechelic RAFT-generated p(NiPAAm), carrying a propargyl function at both ends, suitable as macromolecular "clickable" cross-linker with controlled molecular weight. This hybrid system displays a multiresponsive behavior versus temperature, pH, and ionic strength, maintaining cumulative as well as separate sensitivities to the external stimuli. Hyaluronidase catalyzed degradation of the hydrogels, mimicking the extracellular matrix degradation process, is an additional asset for the use of this class of hydrogels as scaffold. Tumor cells, HT-29, grow on the surface of these hybrid hydrogels more than the healthy ones, as NIH3T3. This finding opens a road to micro- and nano-devices based on hyaluronic acid as a promising biopolymer to pursue localized drug delivery.
Dipartimento di Scienze e Tecnologie Chimiche, Università di Roma "Tor Vergata", Via della Ricerca Scientifica, 00133, Rome, Italy.
Sharad K
SK
Pasale
Barbara
B
Cerroni
Shivkumar V
SV
Ghugare
Gaio
G
Paradossi
D000180:Acrylic Resins / Q000138:chemical synthesis / Q000737:chemistry*; D000818:Animals; D002152:Calorimetry, Differential Scanning; D002417:Cattle; D057930:Click Chemistry / Q000379:methods*; D003911:Dextrans; D055119:Elastic Modulus; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives; D005612:Freeze Drying; D019073:HT29 Cells; D006801:Humans; D006820:Hyaluronic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry*; D006821:Hyaluronoglucosaminidase / Q000378:metabolism; D020100:Hydrogels / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D051379:Mice; D008855:Microscopy, Electron, Scanning; D041681:NIH 3T3 Cells; D044367:Phase Transition; D058105:Polymerization; D013696:Temperature
D000180:Acrylic Resins; D003911:Dextrans; D020100:Hydrogels; C015219:fluorescein isothiocyanate dextran; D006820:Hyaluronic Acid; D006821:Hyaluronoglucosaminidase; D016650:Fluorescein-5-isothiocyanate
RAFT polymerization; click chemistry; controlled drug delivery; hyaluronic acid; hydrogels