Physically crosslinked dextran hydrogels by stereocomplex formation of lactic acid oligomers: degradation and protein release behavior.
Hydrogels, physically crosslinked through stereocomplex formation, were obtained by mixing aqueous solutions of dextran with L-lactic acid grafts and dextran with D-lactic acid grafts. Protein-loaded hydrogels were simply prepared by dissolving the protein in these dextran solutions prior to mixing. It was shown that under physiological conditions the gels are fully degradable. When the gels were exposed to an aqueous buffer solution, they first showed a swelling phase in which their weight increased 2-3 times due to absorption of water, followed by a dissolution phase. The degradation time depended on the composition of the hydrogel, i.e., the number of lactate grafts, the length and polydispersity of the grafts and the initial water content, and varied from 1 to 7 days. Most likely, the degradation of the stereocomplex hydrogel started with hydrolysis of the carbonate ester, which links the lactate graft to dextran. The gels showed a release of the entrapped model proteins (IgG and lysozyme) over 6 days and the kinetics depended on the gel characteristics, such as the polydispersity of the lactate grafts and the initial water content. Lysozyme was mainly released by Fickian diffusion, indicating that its hydrodynamic diameter is smaller than the hydrogel mesh size. On the other hand the release of IgG was governed by diffusion as well as swelling/degradation of the hydrogel. Importantly, the proteins were quantitatively released from the gels and with full preservation of the enzymatic activity of lysozyme, emphasizing the protein-friendly preparation method of the protein-loaded stereocomplex hydrogel.
de Jong
S J
SJ
Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, P.O. Box 80.082, 3508 TB Utrecht, The Netherlands.
van Eerdenbrugh
B
B
van Nostrum
C F
CF
Kettenes-van den Bosch
J J
JJ
Hennink
W E
WE
D000465:Algorithms; D003432:Cross-Linking Reagents; D003692:Delayed-Action Preparations; D003911:Dextrans / Q000737:chemistry*; D004058:Diffusion; D004339:Drug Compounding; D020100:Hydrogels / Q000737:chemistry*; D007074:Immunoglobulin G / Q000737:chemistry; D019344:Lactic Acid / Q000737:chemistry*; D008970:Molecular Weight; D009113:Muramidase / Q000737:chemistry; D010316:Particle Size; D011091:Polyesters; D011108:Polymers / Q000737:chemistry*; D011506:Proteins / Q000737:chemistry*; D012212:Rheology
D003432:Cross-Linking Reagents; D003692:Delayed-Action Preparations; D003911:Dextrans; D020100:Hydrogels; D007074:Immunoglobulin G; D011091:Polyesters; D011108:Polymers; D011506:Proteins; D019344:Lactic Acid; C033616:poly(lactide); D009113:Muramidase