Synthesis and characterisation of inulin-azo hydrogels designed for colon targeting.
The present paper describes the synthesis and characterisation of new hydrogel systems designed for colon targeting. The gels were composed of methacrylated inulin (MA-IN), copolymerized with the aromatic azo agent bis(methacryloylamino)azobenzene (BMAAB) and 2-hydroxyethyl methacrylate (HEMA) or methacrylic acid (MA). The gels were assessed by studying the influence of various parameters on the dynamic and equilibrium degree of swelling. It was shown that the uptake of water in the gels was inversely proportional to the MA-IN feed concentration, the degree of substitution of the inulin backbone, and the concentration of BMAAB. The latter can probably be explained by the hydrophobic nature and rigidity of the aromatic azo agent. Incorporation of the hydrophilic monomers HEMA or MA also reduced the equilibrium degree of swelling. An increasing network density and hydrogen bonding propensity, can suggested to be responsible for this observation. It was shown that water uptake in the hydrogels was controlled by both relaxation and diffusion mechanisms (anomalous behaviour). When the release of the model drug prednisolone was studied in phosphate buffer, it was shown that >80% of the drug was released during the first 3 h from hydrogels of MA-IN:HEMA. Although drug release decreased significantly from MA-IN:HEMA:BMAAB hydrogels, it remained too high: approximately 50% of the drug was released after 5 h. The same observation was made for hydrogels containing MA instead of HEMA. These results clearly point out the difficulty in finding the optimal balance between swelling to allow degradation in the colon (high swelling of the gels) and low premature drug release before the colonic environment is reached (low swelling properties).
Maris
B
B
Katholieke Universiteit Leuven, Laboratorium voor Farmacotechnologie en Biofarmacie, Campus Gasthuisberg (O+N), Herestraat 49, 3000 Leuven, Belgium.
Verheyden
L
L
Van Reeth
K
K
Samyn
C
C
Augustijns
P
P
Kinget
R
R
Van den Mooter
G
G
D000893:Anti-Inflammatory Agents / Q000737:chemistry; D001391:Azo Compounds / Q000737:chemistry*; D002021:Buffers; D003106:Colon / Q000378:metabolism*; D016503:Drug Delivery Systems; D005609:Free Radicals / Q000737:chemistry; D020100:Hydrogels / Q000737:chemistry*; D007444:Inulin / Q000737:chemistry*; D007700:Kinetics; D008689:Methacrylates / Q000737:chemistry; D011239:Prednisolone / Q000737:chemistry; D013696:Temperature
D000893:Anti-Inflammatory Agents; D001391:Azo Compounds; D002021:Buffers; D005609:Free Radicals; D020100:Hydrogels; D008689:Methacrylates; C005044:hydroxyethyl methacrylate; D007444:Inulin; D011239:Prednisolone