The in vitro evaluation of 'azo containing polysaccharide gels' for colon delivery.
This study reports on 'azo-polysaccharide gels', more specifically azo-inulin and azo-dextran gels, for colon drug delivery. Compared with azo-hydrogels which can be only degraded by reduction of the azo-groups, this study evaluates whether, in vitro, azo-polysaccharide gels can be degraded through both reduction of the azo-groups in the crosslinks as well as enzymatic break down of the polysaccharide backbone. The azo-polysaccharide gels were synthesized by radical crosslinking of a mixture of methacrylated inulin or methacrylated dextran and N,N'-bis(methacryloylamino)azobenzene (B(MA)AB) and were characterized by dynamic mechanical analysis and swelling measurements. Azo-dextran gels could be obtained from methacrylated dextran having low degree of substitution but not from lowly substituted methacrylated inulin. Increasing the amount of B(MA)AB resulted in denser azo-inulin and azo-dextran networks. Compared with their swelling in dimethylformamide, all azo-dextran gels became more swollen in water while azo-inulin gels shrank upon exposure to water, indicating a more hydrophobic character of the azo-inulin gels. Break down of the inulin and dextran chains in the azo-polysaccharide gels by inulinase and dextranase, respectively, was observed. However, the degradation of azo-dextran gels by dextranase seemed to be more pronounced than the degradation of the azo-inulin gels by inulinase. In rat caecal content medium, reduction of the azo function in azo-inulin gels was not observed. This may be attributed to a low partitioning of nicotinamide-adenine dinucleotide phosphate (NADP(+)) in the gels.
Stubbe
B
B
Laboratorium voor Algemene Biochemie en Fysische Farmacie, Ghent University, Ghent, Belgium.
Maris
B
B
Van den Mooter
G
G
De Smedt
S C
SC
Demeester
J
J
D000465:Algorithms; D000818:Animals; D001391:Azo Compounds / Q000737:chemistry*; D002432:Cecum / Q000378:metabolism; D003106:Colon / Q000378:metabolism*; D003911:Dextrans / Q000737:chemistry; D016503:Drug Delivery Systems; D005182:Flavin-Adenine Dinucleotide / Q000737:chemistry; D005782:Gels; D006868:Hydrolysis; D066298:In Vitro Techniques; D007444:Inulin / Q000737:chemistry; D008297:Male; D009249:NADP / Q000737:chemistry; D011134:Polysaccharides / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar
D001391:Azo Compounds; D003911:Dextrans; D005782:Gels; D011134:Polysaccharides; D005182:Flavin-Adenine Dinucleotide; D009249:NADP; D007444:Inulin