Degradation behavior of dextran hydrogels composed of positively and negatively charged microspheres.
This paper reports on the degradation behavior of in situ gelling hydrogel matrices composed of positively and negatively charged dextran microspheres. Rheological analysis showed that, once the individual microspheres started to degrade, the hydrogel changed from a mainly elastic to a viscoelastic network. It was shown with gels composed of equal amounts of cationic and anionic microspheres, that both a higher crosslink density of the particles and a decrease in water content of the hydrogels resulted in a slower degradation, ranging from 65 to 140 days. Dispersions containing cationic, neutral or anionic microspheres completely degraded within 30, 55 or 120 days, respectively. The microspheres were loaded with rhodamine-B-dextran and degradation was studied with confocal microscopy and fluorescence spectroscopy. After a lag time of 3 days rhodamine-B-dextran started to release from the positive microspheres with a 50% release after 16 days. In contrast, release of rhodamine-B-dextran from the negative microspheres started after 10 days with a 50% release after 36 days. The faster degradation of the positively charged microspheres as compared to the negatively charged microspheres is attributed to stabilization of the transition state in the hydrolysis process by the protonated tertiary amine groups present in the cationic microspheres. On the other hand, the presence of negatively charged groups causes repulsion of hydroxyl anions resulting in a slower degradation. Combining the oppositely charged microspheres in different ratios makes it possible to tailor the network properties and the degradation behavior of these hydrogels, making them suitable for various applications in drug delivery and tissue engineering.
Van Tomme
Sophie R
SR
Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences (UIPS), University Utrecht, P.O. Box 800082, 3508 TB Utrecht, The Netherlands.
van Nostrum
Cornelus F
CF
de Smedt
Stefaan C
SC
Hennink
Wim E
WE
D000838:Anions; D001672:Biocompatible Materials / Q000737:chemistry*; D002412:Cations; D003432:Cross-Linking Reagents / Q000494:pharmacology; D003911:Dextrans / Q000737:chemistry*; D016503:Drug Delivery Systems; D020100:Hydrogels / Q000737:chemistry*; D008863:Microspheres; D008956:Models, Chemical; D010316:Particle Size; D012235:Rhodamines
D000838:Anions; D001672:Biocompatible Materials; D002412:Cations; D003432:Cross-Linking Reagents; D003911:Dextrans; D020100:Hydrogels; D012235:Rhodamines