Natural polysaccharides have been utilized as additives for oral dosage forms of various medications. Chitosan (CS) has recently been studied as an excellent vehicle for drug delivery because of its biocompatibility and biodegradability. [1][2][3] CS has polycationic properties and forms a film-like complex with polyanionic compounds.4) Therefore, CS acts as an anion exchange resin, and the influence of CS intake on the human body has been studied. 5) In contrast, chitin (CT) has not been used as an additive, although it is both abundant and is the source of CS. 6) One of the reasons for this is that CT scarcely dissolves in most organic or inorganic solvents.Alginic acid is an anionic polysaccharide, which consists of a-L-guluronic acid (G) and b-D-mannuronic acid (M) subunits. Sodium alginate is administered to treat gastric ulcers by reducing gastric acid irritation. Alginate solution quickly forms a gel matrix in the presence of a divalent cation such as Ca 2ϩ and this gelation is known to arise primarily at junctions ("egg-box junctions") in G-G-sequence rich chain regions (G-blocks), rather than M-blocks. Alg-Ca is expected to be used as a vehicle for drug delivery because Alg-Ca is able to incorporate drugs or other polysaccharides within the matrix, and the relationship between drug release and alginate gel bead erosion has been investigated.
7)Colon targeting has recently been studied for drug delivery to the topical region. The release profile of an anti-inflammatory drug such as a steroid from orally administered forms in the gastrointestinal tract may affect the treatment of inflammatory bowel diseases such as Crohn's disease. 8) In the present study, we attempted to prepare Alg-Ca containing polysaccharides, including an alginate hydrolysate, and investigated the effects on the drug release profiles of Alg-Ca under mimic gastrointestinal conditions.
ExperimentalChemicals A model drug, hydrocortisone (HC), was purchased from Wako Pure Chemical Ind. (Osaka, Japan). Sodium alginate (degree of polymerization; 450) was obtained from Nacalai Tesque (Kyoto, Japan), and alginic acid (non-swelling, NS) was obtained from Wako. CT and CS were obtained from Kimitsu Chem. Ind. (Tokyo, Japan) and agar (UP-16) was obtained from Ina Food Co. (Nagano, Japan). All other reagents used were of analytical grade.Viscosity of Alginate Solution Containing Polysaccharide Each polysaccharide was added to 1% sodium alginate solution and well stirred, and then the viscosity of the solution was measured with a Brookfield viscometer 5 times at room temperature (25°C).Hydrolysis of NS NS was partially hydrolyzed (0.3 M HCl, 2 h, 100°C) and the G-and M-blocks were separated by the method of Haug et al.9) Solutions containing each block were precipitated with ethanol after neutralization and centrifuged (3000 rpm, 10 min). The pellet was then washed with ethanol, and dried in vacuo over P 2 O 5 .Preparation of Modified Alg-Ca Alg-Ca was prepared as follows: One percent sodium alginate was dissolved in distilled and demineralized wa...