Methyl-DEAE-dextran: a candidate biomaterial.
The full quaternisation of DEAE-dextran was successfully attempted and an application of the quaternised product was suggested. Commercial DEAE-dextran was reacted with iodomethane at 60 degrees C in the presence of NaOH. The raw product was purified by dialysis, during which the iodide ion was replaced by chloride. N-methylation and O-methylation resulted from the reaction. A second methylation step produced no further changes in the molecule. Alkalimetry indicated the absence of amino groups in the methylated polymer molecule, thus testifying to a complete quaternisation. N-acetylcysteine (AcCy) was neutralised with the polymer in the hydroxide form, thus obtaining the methyl DEAE-dextran salt of AcCy (Me-DEAE-dextran/AcCy), whereby an ophthalmic formulation for the treatment of the dry eye syndrome was prepared. For comparison, the neutral AcCy salt of commercial DEAE-dextran (DEAE-dextran/AcCy) was prepared. The AcCy content in Me-DEAE-dextran/AcCy was higher than in DEAE-dextran/AcCy (23 vs 13%), while the viscosity of a solution containing the salt concentration corresponding to the therapeutic AcCy concentration (4%w/v) was lower with the former compared to the latter salt (20.5 vs 23.9 mPa s). Both solutions were ipotonic (245 mOsm/kg), whereas the commercial Tirocular is strongly hypertonic (900 mOsm/kg) and irritant.
Department of Bioorganic Chemistry and Biopharmaceutics, University of Pisa, Pisa, Italy. zambito@farm.unipi.it
Ylenia
Y
Zambito
Andrea
A
Baggiani
Vera
V
Carelli
Maria Francesca
MF
Serafini
Giacomo
G
Di Colo
D000111:Acetylcysteine / Q000008:administration & dosage* / Q000737:chemistry*; D001672:Biocompatible Materials / Q000737:chemistry*; D003637:DEAE-Dextran / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000379:methods*; D015352:Dry Eye Syndromes / Q000188:drug therapy; D006801:Humans; D020100:Hydrogels / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D008422:Materials Testing; D008745:Methylation; D009883:Ophthalmic Solutions / Q000008:administration & dosage* / Q000737:chemistry*
D001672:Biocompatible Materials; D020100:Hydrogels; D009883:Ophthalmic Solutions; D003637:DEAE-Dextran; D000111:Acetylcysteine