• BMB Reports
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• v.40 no.4
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• pp.562-570
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• 2007

Soluble or cell-bound IL-1 receptor accessory protein (IL-1RAcP) does not bind IL-1 but rather forms a complex with IL-1 and IL-1 receptor type I (IL-1RI) resulting in signal transduction. Synthetic peptides to various regions in the Ig-like domains of IL-1RAcP were used to produce antibodies and these antibodies were affinity-purified using the respective antigens. An anti-peptide-4 antibody which targets domain III inhibited 70% of IL-$1\beta$-induced productions of IL-6 and PGE2 from 3T3-L1 cells. Anti-peptide-2 or 3 also inhibited IL-1-induced IL-6 production by 30%. However, antipeptide-1 which is directed against domain I had no effect. The antibody was more effective against IL-$1\beta$ compared to IL-$1\alpha$. IL-1-induced IL-6 production was augmented by coincubation with PGE2. The COX inhibitor ibuprofen blocked IL-1-induced IL-6 and PGE2 production. These results confirm that IL-1RAcP is essential for IL-1 signaling and that increased production of IL-6 by IL-1 needs the co-induction of PGE2. However, the effect of PGE2 is independent of expressions of IL-1RI and IL-1RAcP. Our data suggest that domain III of IL-1RAcP may be involved in the formation or stabilization of the IL-1RI/IL-1 complex by binding to epitopes on domain III of the IL-1RI created following IL-1 binding to the IL-1RI.

• Journal of Pharmaceutical Investigation
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• v.26 no.3
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• pp.187-192
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• 1996

The matrix tablet containing sodium alginate and $CaHPO_4$ can release drugs in a controlled fashion from hydrogel with gelling and swelling due to their interaction as water penetrates the matrices of the tablet. The purpose of this study was to evaluate release characteristics of the matrix tablet varying the amount of sodium alginate, $CaHPO_4$ and other excipients such as chitosan, hydroxypropyl methylcellulose (HPMC) and $Eudragit^{\circledR}$ RS100 in the simulated gastric and intestinal fluid. The practically soluble ibuprofen was used as a model drug. The release profiles of matrix tablet in the gastric fluid as a function of sodium alginate/$CaHPO_4$ ratio was not pronounced because of low solubility of drug and stability of alginate matrices. However, release rate of drug from the matrix tablet in the intestinal fluid was largely changed when sodium alginate/$CaHPO_4$ ratio was increased, suggesting that the ratio of sodium alginate/$CaHPO_4$ was an important factor to control the gelling and swelling of the matrix tablet. The incorporation of other excipients into the matrix tablet also influenced the release rate of drug. The chitosan and HPMC decreased the release rate of drug. No release of drug was occurred when $Eudragit^{\circledR}$ RS100 was added into the tablet. The retarded release of matrix tablet when excipients were added resulted from the hindrance of swelling and gelling of the matrix tablet containing sodium alginate and $CaHPO_4$. The hardness and bulk density of the matrix tablet was not correlated with release rate of drug in the study. From these findings, the ratio of sodium alginate and $CaHPO_4$ in the matrix tablet in addition to incorporation of excipients could be very important to control the release rate of drug in dosage form design.

• Archives of Pharmacal Research
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• v.21 no.6
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• pp.645-650
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• 1998

The dual drug-loaded alginate beads simultaneously containing drug in inner and outer layers were prepared by dropping plain (single-layered) alginate beads into $CaCl_2$ solution. The release characteristics were evaluated in simulated gastric fluid for 2 h followed by intestinal fluids thereafter for 12 h. The surface morphology and cross section of dual drug-loaded alginate beads was also investigated using scanning electron microscope (SEM). The poorlv water-soluble ibuprofen was chosen as a model drug. The surface of single-layered and dual drug-loaded alginate beads showed very crude and roughness, showing aggregated particles, surface cracks and rough crystals. The thickness of dual drug-loaded alginate beads surrounded by outer layer was ranged from about 57 to 329mcm. The distinct chasm between inner and outer layers was also observed. In case of single-layered alginate bead, the drug was not released in gastric fluid but was largely released in intestinal fluid. However, the release rate decreased as the reinforcing $Eudragit^{\circledR}$ polymer contents increased. When the plasticizers were added into polymer, the release rate largely decreased. The release rate of dual drug-loaded alginate beads was stable in gastric fluid for 2 h but largely increased when switched in intestinal fluid. The drug linearly released for 4 h followed by another linear release thereafter, showing a distinct biphasic release characteristics. There was a difference in the release profiles between single-layered and dual drug-loaded alginate beads due to their structural shape. However, this biphasic release profiles were modified by varying formulation compositions of inner and outer layer of alginate beads. The release rate of dual drug-loaded alginate beads slightly decreased when the outer layer was reinforced with $Eudragit^{\circledR}$ RS1OO polymers. In case of dual drug-loaded alginate beads with polymer-reinforced outer layer only, the initial amount of druc released was low but the initial release rate (slope) was higher due to more swellable inner cores when compared to polymer-reinforced inner cores. The current dual drug-loaded alginate beads may be used to deliver the drugs in a time dependent manner.