A novel strategy for encapsulation and release of proteins: hydrogels and microgels with acid-labile acetal cross-linkers.
A new acid-labile acetal cross-linker was synthesized and used to prepare protein-loaded hydrogels and microgels. This cross-linker undergoes an acid-catalyzed degradation with a half-life of 5.5 min at pH 5.0 and 24 h at pH 7.4. Protein-loaded hydrogels were synthesized with this cross-linker, and their release profiles were measured as a function of pH. Hydrogels made with the acetal cross-linker release their contents in a pH-dependent manner. The acetal cross-linker was also used to synthesize microgels with sizes between 1 and 10 mum, a range suitable for phagocytosis. The unique acid sensitivity of the acetal cross-linker should make it a useful synthetic intermediate in the design of acid-sensitive drug or gene delivery systems.
Murthy
Niren
N
Center for New Directions in Organic Synthesis, Department of Chemistry, University of California, Berkeley, California 94720-1460, USA.
Thng
Yi X
YX
Schuck
Stephany
S
Xu
Ming C
MC
Fréchet
Jean M J
JM
D000080:Acetals / Q000138:chemical synthesis / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D003432:Cross-Linking Reagents / Q000138:chemical synthesis / Q000737:chemistry; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives* / Q000737:chemistry; D020100:Hydrogels / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D010316:Particle Size; D011506:Proteins / Q000737:chemistry*; D012710:Serum Albumin, Bovine / Q000737:chemistry
D000080:Acetals; D003432:Cross-Linking Reagents; D020100:Hydrogels; D011506:Proteins; C039217:fluorescein isothiocyanate bovine serum albumin; D012710:Serum Albumin, Bovine; D016650:Fluorescein-5-isothiocyanate