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Self‐assembling cyclodextrin based hydrogels for the sustained delivery of hydrophobic drugs
Author(s) -
DaoudMahammed S.,
Grossiord J. L.,
Bergua T.,
Amiel C.,
Couvreur P.,
Gref R.
Publication year - 2007
Publication title -
journal of biomedical materials research part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.849
H-Index - 150
eISSN - 1552-4965
pISSN - 1549-3296
DOI - 10.1002/jbm.a.31674
Subject(s) - materials science , biocompatibility , self healing hydrogels , polymer , cyclodextrin , rheology , aqueous solution , viscoelasticity , dynamic mechanical analysis , dextran , chemical engineering , polymer chemistry , chromatography , organic chemistry , chemistry , composite material , engineering , metallurgy
Abstract This study aims to investigate the rheological properties of self‐assembling gels containing cyclodextrins with potential application as injectable matrix for the sustained delivery of poorly soluble drugs. The ability of these gels to entrap two hydrophobic molecules, benzophenone (BZ) and tamoxifen (TM), and to allow their in vitro sustained release was evaluated. In view of their future pharmaceutical use, gels were sterilized by high hydrostatic pressures (HHP) and tested for their biocompatibility. The gels formed instantaneously at room temperature, by mixing the aqueous solutions of two polymers: a β‐cyclodextrin polymer (pβCD) and a hydrophobically modified dextran by grafting alkyl side chains (MD). MD‐pβCD gels presented a viscoelastic behavior under low shear, characterized by constant values of the loss modulus G ″ and the storage modulus G ′. The most stable gels were obtained for a total polymer concentration C p of 6.6% and 7.5% (w/w), and a polymer ratio MD/pβCD of 50/50 and 33/67 (w/w). BZ and TM were successfully incorporated into MD‐pβCD gels with loading efficiencies as high as 90%. In vitro , TM and BZ were released gradually from the gel matrix with less than 25% and 75% release, respectively, after 6 days incubation. HHP treatment did not modify the rheological characteristics of MD‐pβCD gels. Moreover, the low toxicity of these gels after intramuscular administration in rabbits makes them promising injectable devices for local delivery of drugs. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res 2008