Influence of dialkyne structure on the properties of new click-gels based on hyaluronic acid.
Hydrogels have been widely used in tissue engineering as a support for tissue formation and/or to deliver drug locally. A novel procedure for the in situ rapid chemical gelation of aqueous solutions of hyaluronan (HA) was employed. HA was functionalised with an arm bearing a terminal azido group (HAAA). When HAAA was mixed with a series of dialkyne reagents of different length, a 1,3-dipolar cycloaddition ("click-chemistry") reaction took place in the presence of catalytic amount of Cu(I) resulting in fast gelation at room temperature. The resulting gels were characterised in terms of degree of cross-linking by (1)H HR-MAS NMR. The kinetic of gelation and the determination of elastic moduli as well as the degree of swelling and the controlled release of a model drug, were studied as a function of chemical nature of the dialkyne group, catalyst concentration, HAAA concentration and temperature. All these variables allowed the swelling ratio and the extent of release of a drug, doxorubicin, entrapped within the gel, to be modulated. In all cases the kinetic of release reached the stationary state within 150 h. The height of the plateau was dependent on the overall (chemical and topological) degree of cross-linking.
Testa
Gabriella
G
Department of Chemistry, Sapienza University of Rome, P.le A.Moro 5, 00185 Rome, Italy.
Di Meo
Chiara
C
Nardecchia
Stefania
S
Capitani
Donatella
D
Mannina
Luisa
L
Lamanna
Raffaele
R
Barbetta
Andrea
A
Dentini
Mariella
M
D000480:Alkynes / Q000737:chemistry*; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003432:Cross-Linking Reagents / Q000737:chemistry; D003692:Delayed-Action Preparations; D004317:Doxorubicin / Q000008:administration & dosage*; D016503:Drug Delivery Systems; D006820:Hyaluronic Acid / Q000737:chemistry*; D020100:Hydrogels; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D013329:Structure-Activity Relationship; D013696:Temperature; D023822:Tissue Engineering / Q000379:methods*
D000480:Alkynes; D000903:Antibiotics, Antineoplastic; D003432:Cross-Linking Reagents; D003692:Delayed-Action Preparations; D020100:Hydrogels; D004317:Doxorubicin; D006820:Hyaluronic Acid