The effect of network charge on the immobilization and release of proteins from chemically crosslinked dextran hydrogels.
Size is the main protein characteristic that determines its release from non-degrading neutral hydrogels. The effect of network charge on the release of proteins has not been studied systematically so far. Therefore, we investigated the release of proteins from charged hydrogels that were obtained by co-polymerization of methacrylated dextran (Dex-MA) with either methacrylic acid (MA) or 2-N,N-dimethylaminoethyl methacrylate (DMAEMA). These hydrogels are stable under physiological conditions. The effect of incorporation of the charged monomers on hydrogel charge, equilibrium swelling, and release of model proteins was assessed at both low (10mM HEPES) and physiological ionic strength (HEPES buffered saline, HBS). Model proteins were chosen on the basis of their charge at physiological pH; bovine serum albumin (BSA, negatively charged), myoglobin (neutral), and cytochrome C (positively charged). Interestingly, as opposed to myoglobin, both charged proteins were fully immobilized in the networks with opposite charge by electrostatic interaction at low ionic strength. On the other hand, at physiological ionic strength, the percentage of immobilized protein depended on the charge density of the hydrogel. For all proteins, the diffusion coefficient of the mobile fractions was not affected by opposite network charge. However, the release rate of BSA from similarly (negatively) charged networks significantly increased when a relatively high amount of charged monomers was incorporated. We conclude that incorporation of charge in a hydrogel network is suited as a tool for the immobilization of proteins and triggered release by increasing ionic strength.
Schillemans
Joris P
JP
Department of Pharmaceutics, Utrecht University, Utrecht, The Netherlands.
Hennink
Wim E
WE
van Nostrum
Cornelus F
CF
D000818:Animals; D002417:Cattle; D003911:Dextrans / Q000737:chemistry*; D004058:Diffusion; D006531:HEPES; D006736:Horses; D020100:Hydrogels / Q000138:chemical synthesis / Q000737:chemistry*; D008689:Methacrylates / Q000737:chemistry*; D009994:Osmolar Concentration; D058105:Polymerization; D011506:Proteins / Q000737:chemistry*; D012710:Serum Albumin, Bovine
D003911:Dextrans; D020100:Hydrogels; D008689:Methacrylates; D011506:Proteins; C514458:methacrylated dextran; C008384:methacrylic acid; D012710:Serum Albumin, Bovine; D006531:HEPES