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Mobility of model proteins in hydrogels composed of oppositely charged dextran microspheres studied by protein release and fluorescence recovery after photobleaching.
- Source :
-
Journal of controlled release : official journal of the Controlled Release Society [J Control Release] 2005 Dec 10; Vol. 110 (1), pp. 67-78. Date of Electronic Publication: 2005 Oct 25. - Publication Year :
- 2005
-
Abstract
- In this paper, the release of proteins from a novel self-gelling hydrogel based on biodegradable dextran microspheres is investigated. The protein-loaded macroscopic gels are obtained by hydration of mixtures of oppositely charged hydroxyethyl methacrylate-derivatized dextran microspheres with a protein solution. In media of low ionic strength (100 mM Hepes pH 7.0) it was found that the release of the entrapped model proteins (lysozyme, BSA and IgG) was slower than in saline (150 mM NaCl, 100 mM Hepes pH 7.0). The reason behind this observation is that substantial adsorption of the proteins onto the microspheres' surface and/or absorption in the microspheres takes place. Confocal images showed that independent of their crosslink density the microspheres are impermeable for BSA and IgG. BSA, bearing a negative charge at neutral pH, was adsorbed onto the surface of positively charged microspheres. Lysozyme, which is positively charged at neutral pH, was able to penetrate into the negatively charged microspheres. In saline, the gels showed continuous release of the different proteins for 25 to 60 days. Importantly, lysozyme was quantitatively and with full preservation of its enzymatic activity released in about 25 days. This emphasizes the protein friendly technology to prepare the protein-loaded gels. Mathematical modeling revealed that protein release followed Fick's second law, indicating that the systems are primarily diffusion controlled. These results show that these hydrogels are very suitable as injectable matrix for diffusion-controlled delivery of pharmaceutically active proteins.
- Subjects :
- Adsorption
Diffusion
Fluorescence Recovery After Photobleaching
HEPES chemistry
Immunoglobulin G chemistry
Methacrylates chemistry
Microscopy, Confocal
Microspheres
Motion
Muramidase chemistry
Osmolar Concentration
Proteins administration & dosage
Serum Albumin, Bovine chemistry
Time Factors
Water chemistry
Dextrans chemistry
Drug Carriers chemistry
Hydrogels chemistry
Proteins chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 0168-3659
- Volume :
- 110
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Journal of controlled release : official journal of the Controlled Release Society
- Publication Type :
- Academic Journal
- Accession number :
- 16253375
- Full Text :
- https://doi.org/10.1016/j.jconrel.2005.09.005