Biomedical subjects

Akira Yamamoto

Publications and source records attributed to Akira Yamamoto.

At least 37 records · Page 2Linked to original sources

PubMed2006

Colon-specific delivery and enhanced colonic absorption of [Asu(1,7)]-eel calcitonin using chitosan capsules containing various additives in rats.

The objective of this study was to estimate the colon-specific delivery of [Asu1,7]-eel calcitonin (ECT) using chitosan capsules in rats. The intestinal absorption of ECT was evaluated by measuring the plasma calcium levels after oral administration of the chitosan capsules containing ECT and different combinations of additives. The same combinations were investigated by an in situ absorption experiment prior to in vivo administration of capsules. A marked decrease in plasma calcium levels was observed following the oral administration of chitosan capsules containing ECT, S-nitroso-N-acetyl-dl-penicillamine (SNAP), sodium glycocholate, bacitracin and aprotinin (pharmacological availability (PA)% = 6.344%), as compared with capsules containing only ECT (PA% = 0.551%) or capsules containing ECT with SNAP only (PA% = 1.651%). The hypocalcemic effect started 6-8 h after oral administration of capsules and sustained for 24 h. These findings suggest that colon-specific delivery of ECT can be achieved using chitosan capsules and these additives may be useful for improving the colonic absorption of ECT in rats.

Animals↗

PubMed2006

Evaluation of tris-acryl gelatin microsphere embolization with monochromatic X Rays: comparison with polyvinyl alcohol particles.

PURPOSE: Imaging of blood vessels 30 mum or smaller can be achieved with use of monochromatic x rays. The purpose of the present investigation was to use this method to evaluate the in vivo primary embolic effect of tris-acryl gelatin microspheres and polyvinyl alcohol (PVA) particles in small blood vessels, and specifically to assess the distribution of these particles and the resulting changes in circulation. MATERIALS AND METHODS: Twelve rabbits were divided into four groups: group 1 (PVA particles, 90-180 mum; n = 3), group 2 (tris-acryl gelatin microspheres, 40-120 mum; n = 3), group 3 (PVA, 300-500 mum; n = 3), and group 4 (tris-acryl gelatin microspheres, 300-500 mum; n = 3). After microangiography with monochromatic x rays, embolization was performed in normal auricular blood vessels, and immediately thereafter, postembolization microangiography was performed. Images acquired before and after embolization with the four embolic agents were compared, and the diameters of embolized blood vessels were measured. The mean embolized vascular diameter and its ratio to the midrange particle size of the embolic agent were calculated. RESULTS: Tris-acryl gelatin microspheres did not aggregate and tended to lodge in vessels close in size to the individual particle size, whereas PVA particles aggregated in vessels larger than the individual particle size. For tris-acryl gelatin microspheres, no blood flow was noted peripheral to the embolized region, whereas for PVA particles, blood flow was noted in regions peripheral to the embolized region. CONCLUSIONS: Monochromatic x rays allow direct visualization of in vivo embolic properties. This technique holds promise for comparative studies of embolic agents.

Acrylic Resins↗

PubMed2006

Vaccine efficacy of fusogenic liposomes containing tumor cell-lysate against murine B16BL6 melanoma.

Recent advances in tumor immunology have facilitated the development of cancer immunotherapy targeting tumor-associated antigens (TAAs). However, because TAAs were identified in only a few types of human cancer, novel vaccine strategies that utilize tumor cell-lysate (TCL), including unidentified TAAs as an antigen source, are needed. Herein, we describe the utility of fusogenic liposomes (FLs) as TCL-delivery carriers for both ex vivo dendritic cell-based vaccination and in vivo direct immunization in the murine B16BL6 melanoma model. As a result, both in vivo direct immunization and ex vivo immunization induced anti-B16 melanoma prophylactic effects. Ex vivo dendritic cell (DC)-mediated vaccination strategy exert more potent anti-tumor effect than direct immunization. Our results suggest that this flexible system is a promising approach for the development of versatile cancer immunotherapy regimes.

Animals↗

PubMed2006

Excellent absorption enhancing characteristics of NO donors for improving the intestinal absorption of poorly absorbable compound compared with conventional absorption enhancers.

The characteristics of NO donors, NOC5 [3-(2-hydroxy-1-(1-methylethyl-2-nitrosohydrazino)-1-propanamine), NOC12 [N-ethyl-2-(1-ethyl-2-hydroxy-2-nitrosohydrazino)-ethanamine] and SNAP [S-nitroso-N-acetyl-DL-penicillamine] as absorption enhancers for poorly absorbable drugs were examined in rats using an in situ closed loop method. They were compared with a group of conventional absorption enhancers including sodium glycocholate (NaGC), sodium caprate (NaCap), sodium salicylate (NaSal) and n-dodecyl-beta-D-maltopyranoside (LM). 5(6)-carboxyfluorescein (CF) was used as a model drug to investigate effectiveness, site-dependency, and concentration-dependency of the tested enhancers. Overall, the NO donors can improve the intestinal absorption of CF at low concentration (5 mM), whereas higher concentration was required for the conventional absorption enhancers to elicit the absorption enhancing effect. In the small intestine, SNAP was the most effective absorption enhancers, although its concentration (5 mM) was lower than the conventional absorption enhancers (20 mM). On the other hand, LM and NaCap as well as the three NO donors were effective to improve the colonic absorption of CF. In the regional difference in the absorption enhancing effects, the NO donors showed significant effects in all intestinal regions, whereas we observed a regional difference in the absorption enhancing effect of the other conventional absorption enhancers. In the conventional enhancers, the absorption enhancing effects were generally greater in the large intestine than those in the small intestine. LM and NaCap were ineffective in the jejunum, although they were effective for improving the absorption of CF in the colon. NaSal was ineffective in both the jejunum and the colon. The absorption enhancement produced by NO donors was greatly affected by increasing the enhancer concentration from 3 to 5 mM, but only a slight increase was obtained when the concentration was raised to 10 mM. Similar results were obtained for the other enhancers over the range of 10 to 20 mM, but the absorption enhancing effects of these enhancers were almost saturated above these concentrations. These results suggest that NO donors possess excellent effectiveness as absorption enhancers for poorly absorbable drugs compared with the conventional enhancers. They can enhance intestinal absorption of CF from all intestinal regions and they are effective at very low concentrations.

Adjuvants, Pharmaceutic↗

PubMed2006

What kinds of substrates show P-glycoprotein-dependent intestinal absorption? Comparison of verapamil with vinblastine.

The influence of P-glycoprotein (P-gp) on intestinal absorption of drugs was investigated by comparison of the uptakes of two P-gp substrates, verapamil and vinblastine, using intestinal segments of wild-type and mdr1a/1b gene-deficient (mdr1a/1b(-/-)) mice, and Caco-2 cells. When [(3)H]vinblastine was injected into intestinal segments of wild-type mice, vinblastine was absorbed from duodenum and ileum, but not from jejunum. This difference among intestinal regions could not be explained by segmental differences of mdr1a mRNA expression. In Caco-2 cells, it was found that vinblastine had a high value of efflux/influx ratio (an index of affinity for P-gp) of 12.1, and a low permeability of less than 1 x 10(-6) cm/sec. The corresponding values for verapamil were 4.9 and 10.6 x 10(-6) cm/sec, respectively. After oral administration of [(3)H]vinblastine to mice, the maximum concentration (C(max)) and the area under the plasma concentration time-curve from time 0 to 24 hr (AUC(0-24 hr)) for mdr1a/1b(-/-) mice were 1.5 times greater than those for wild-type mice, while these parameters were not significantly different between the two strains in the case of [(3)H]verapamil. Therefore, P-gp substrates may be classified into at least two types, i.e., verapamil-type, for which the intestinal absorption is unaffected by P-gp, and vinblastine-type, for which the intestinal absorption is influenced by P-gp. Vinblastine-type P-gp substrates, with low permeability and high affinity for P-gp, would be unfavorable candidates for oral drugs.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2006

Influence of moisture conditions on dentin bond strength of single-step self-etch adhesive systems.

This study was conducted to clarify the influence of dentin surface moisture on bond strength of single-step self-etch adhesive systems. The adhesive systems used were Adper Prompt L-Pop (AP), Clearfil tri-S Bond (CT), Fluoro Bond Shake One (FB), G-Bond (GB), and One-Up Bond F Plus (OF). Bovine mandibular incisors were wet-ground with #600 SiC to expose the labial dentin. After rinsing with tap water, the dentin surface was dried with air for 10 sec (Dry condition) or blotted (Wet condition). Adhesives were applied according to each manufacturer's instructions, followed by resin composite polymerization. Ten samples per test group were stored in distilled water at 37 degrees C for 24 h, then shear tested at a crosshead speed of 1.0 mm/min. The data were analyzed by Student's t test and Tukey HSD test at a probability level of 0.05. The mean bond strengths for Dry condition ranged from 13.9 MPa to 18.2 MPa, and those for Wet condition ranged from 7.1 MPa to 18.4 MPa. Significantly lower bond strengths were obtained for the Wet condition for GB, FB, and OF. Failure after the test was commonly due to adhesive breakdown associated with partial cohesive failure in the dentin. These data suggest that air-drying of the dentin surface is appropriate for the adhesive systems tested.

Acid Etching, Dental↗

PubMed2006

Influence of light intensity on dentin bond strength of self-etch systems.

The purpose of this study was to investigate the influence of light intensity on dentin bond strengths of four self-etch adhesive systems. The light intensities used to polymerize specimens were controlled at levels of 150, 300, 600, and 900 mW/cm2. The two-step self-etch adhesive systems Imperva Fluoro Bond and Mac Bond II, and the one-step self-etch systems Fluoro Bond Shake-One and One-Up Bond F Plus were used with their corresponding light-cured resins. Labial surfaces of lower bovine incisors were ground with #600 grit SiC paper to expose the dentin. The dentin surfaces were treated according to each manufacturer's instructions and bonded with resin composites. A shear bond strength test was performed and the data were analyzed by one-way ANOVA followed by Newman-Keuls multiple comparison at a level of 0.05. Statistical analysis of the data indicated that light intensity affected the dentin bond strengths of the adhesive systems tested. Significantly lower bond strengths were obtained by exposure to 150 mW/cm2, and there were no differences between the bond strengths obtained at 600 and 900 mW/cm2 for all the adhesive systems used. Further research will be required to clarify the irradiance-dependent properties of light-cured resin adhesive systems.

Acid Etching, Dental↗

PubMed2006

Prevalence of metabolic syndrome in the general Japanese population in 2000.

To determine the prevalence of metabolic syndrome in the Japanese general population, we analyzed data from a nationwide survey conducted in 2000. According to the Japanese new diagnostic criteria for metabolic syndrome in 2005, we analyzed 3,264 people aged from 20 to 79 (men, 1,917; women, 1,347) from the total participants. The incidence of metabolic syndrome was 7.8%. Men had a higher incidence (12.1%) than women (1.7%). Most of the women satisfying the criteria were 50 years old or over, while the incidence in men started to rise from their 30s. When we applied the criteria of Adult Treatment Panel III, the incidence was about 3-fold higher. In this population visceral obesity was associated with metabolic abnormalities, such as higher LDL-cholesterol, triglyceride, glucose, and blood pressure and lower HDL-cholesterol. Thus we determined the incidence of metabolic syndrome and each metabolic abnormality in the Japanese general population in 2000 and found an association of visceral obesity with metabolic abnormalities. Intervention to reduce the incidence of metabolic syndrome in Japan is necessary to reduce the risk of cardiovascular disease.

Adult↗

PubMed2006

[Changing behavior of estrogen and progesterone receptors with metastasis or recurrence of breast cancer].

Changes in level of estrogen receptor (ER) and progesterone receptor (PgR) and their affecting factors were studied with metastasis or recurrence of breast cancer. Since 1983, from 177 patients, 443 specimens were obtained and 244 simultaneous and 122 sequential pairs were compared. The consistency rate was 81% for both ER and PgR with simultaneous comparison,and 69% for ER and 71% for PgR with sequential comparison, mainly due to positive-to-negative change, and less than 10% of negative-to-positive change. Positive-to-negative change was prominent with intervening endocrine treatment, and it was significant (p=0.015) for ER by multiple regression analysis of age, interval of sampling and from prior surgery, intervening chemotherapy, endocrine therapy and human epidermal growth factor receptor 2 (HER 2). Based on recent data of ER and PgR, feasible treatment seems to be planned, because about 30% of them are different from that of primary lesion.

Antineoplastic Agents, Hormonal↗

PubMed2006

18F-FDG small-animal PET for monitoring the therapeutic effect of CT-guided radiofrequency ablation on implanted VX2 lung tumors in rabbits.

UNLABELLED: The primary goals of this study were to investigate the behavior of normal lung tissues after radiofrequency ablation (RFA) and to determine the suitability of 18F-FDG PET, using a dedicated small-animal scanner, for monitoring the early therapeutic effects of RFA on VX2 lung tumors (VX2s) in rabbits. METHODS: Fourteen Japanese white rabbits with normal lungs underwent RFA, followed by 18F-FDG PET at 1 d and at 1, 2, 4, and 8 wk. In addition, 7 rabbits with untreated VX2s underwent 18F-FDG PET, and 13 rabbits with RFA-treated VX2s underwent 18F-FDG PET at 1 d (n = 7) or 1 wk (n = 6) after the treatment. RESULTS: After RFA of normal lungs, ring-shaped accumulations of 18F-FDG, which coincided with inflammation caused by ablation, were observed. The mean early- (40-60 min after injection) and delayed (100-120 min)-phase ablated lesion-to-muscle ratios were, respectively, 2.9 +/- 1.0 and 3.3 +/- 0.8 (1 d), 4.1 +/- 0.6 and 5.2 +/- 0.9 (1 wk), 4.1 +/- 1.0 and 5.3 +/- 1.5 (2 wk), 3.1 +/- 0.5 and 3.6 +/- 1.1 (4 wk), and 1.8 +/- 0.1 and 2.3 +/- 0.1 (8 wk). At 4 and 8 wk, the uptake was less than that at 1 and 2 wk (P < 0.05). VX2s showed mean tumor-to-muscle ratios of 6.6 +/- 2.1 and 8.6 +/- 3.3 at the early and delayed phases, respectively. For ablated tumors, the respective ratios were 0.8 +/- 0.4 and 1.1 +/- 0.7 (1 d) and 1.2 +/- 0.5 and 1.5 +/- 0.7 (1 wk). These values were significantly lower than those for nonablated tumors (P < 0.001). Histopathologic examination confirmed the absence of viable tumors. 18F-FDG accumulation around ablated tumors reflected thermally damaged normal tissues and was significantly lower than that of control VX2s (P < 0.01). CONCLUSION: Our data suggest that 18F-FDG PET is promising for evaluating the therapeutic response of lung malignancies to RFA: Accumulation of 18F-FDG in surrounding normal tissues appears to be time dependent, and the data suggest that, clinically, 18F-FDG PET should be performed 4 wk or more after RFA. Delayed-phase images seem to better distinguish tumor from inflammation than do early-phase images.

Animals↗

PubMed2005

Whole brain magnetization transfer histogram analysis of pediatric acute lymphoblastic leukemia patients receiving intrathecal methotrexate therapy.

BACKGROUND AND PURPOSE: The purpose of this prospective study was to evaluate the hypothesis that magnetization transfer ratio (MTR) histogram analysis of the whole brain could detect early and subtle brain changes nonapparent on conventional magnetic resonance imaging (MRI) in children with acute lymphoblastic leukemia (ALL) receiving methotrexate (MTX) therapy. MATERIALS AND METHODS: Subjects in this prospective study comprised 10 children with ALL (mean age, 6 years; range, 0-16 years). In addition to conventional MRI, magnetization transfer images were obtained before and after intrathecal and intravenous MTX therapy. MTR values were calculated and plotted as a histogram, and peak height and location were calculated. Differences in peak height and location between pre- and post-MTX therapy scans were statistically analyzed. Conventional MRI was evaluated for abnormal signal area in white matter. RESULTS: MTR peak height was significantly lower on post-MTX therapy scans than on pre-MTX therapy scans (p = 0.002). No significant differences in peak location were identified between pre- and post-chemotherapy imaging. No abnormal signals were noted in white matter on either pre- or post-MTX therapy conventional MRI. CONCLUSIONS: This study demonstrates that MTR histogram analysis allows better detection of early and subtle brain changes in ALL patients who receive MTX therapy than conventional MRI.

Adolescent↗

PubMed2005

Functional characterization of Na+-independent choline transport in primary cultures of neurons from mouse cerebral cortex.

We report here the functional characteristics of Na+-independent choline transport system in primary cultures of neurons from mouse cerebral cortex. Na+-independent choline transport was saturable with a Michaelis constant (Kt) of 26.7+/-1.2 microM and a maximal velocity (Vmax) of 1.04+/-0.02 nmol/mg protein/10 min. Choline uptake was significantly influenced by extracellular pH and by membrane depolarization. This uptake system was inhibited by various organic cations including unlabeled choline, guanidine, diphenhydramine and the choline analog hemicholinium-3. However, the prototypical organic cation tetraethylammonium and cimetidine showed very little affinity for the Na+-independent choline uptake system in neurons. These results indicate that mouse cerebrocortical neurons express a Na+-independent, high-affinity choline transport system. RT-PCR revealed that choline transporter-like protein 1 (CTL1) and its spliced variant CTL1a, which have been reported to be novel Na+-independent choline transporter, are expressed in mouse cerebrocortical neurons. The Na+-independent transport properties of choline in mouse neurons is similar or identical to that of CTL1 and/or CTL1a. This choline transport system seems to have relevance not only for neuronal physiology but also for the uptake of pharmacologically important organic cation drugs.

Animals↗

PubMed2005

Functional characteristics of H+ -dependent nicotinate transport in primary cultures of astrocytes from rat cerebral cortex.

In the present study, we report the characteristics of H(+)-coupled nicotinate transport in primary cultures of astrocytes from rat cerebral cortex. The [(3)H]nicotinate transport in rat astrocytes increased up to a pH 5.5. The nicotinic acid uptake at pH 6.0 was both energy-dependent and saturable with a Michaelis constant (K(t)) of 2.8+/-0.4 mM and the maximal uptake rate (V(max)) of 31+/-3.2 nmol/mg protein/10 min. This process was reduced by a protonophore, carbonylcyanide p-trifluoromethoxyphenylhydrazone, and a typical monocarboxylate transporter (MCT) inhibitor, alpha-cyano-4-hydroxycinnamic acid, suggesting that nicotinate uptake by rat astrocytes is mediated by H(+)-coupled monocarboxylate transport system. [(3)H]Nicotinate transport in rat astrocytes was significantly inhibited by various monocarboxylic acids such as l-lactic acid and pyruvic acid with a relatively low affinity (K(i)>10 mM). On the other hand, the uptake process of l-lactic acid was also saturable with a high-affinity component (K(t)=0.27 mM) and a low-affinity component (K(t)=35.9 mM). Reverse transcription-PCR and Western blot analyses revealed that three MCT subtypes, MCT1/Slc16a1, MCT2/Slc16a7, and MCT4/Slc16a3, were expressed in these cells. Because l-lactate reduced to 67% of the nicotinate uptake even at 10mM, it is unlikely that nicotinate uptake in rat astrocytes is mediated by MCT1 and/or MCT2. These results provide biochemical evidence of a H(+)-coupled and saturable transport system, presumed to be a low-affinity monocarboxylate transporter MCT4 or other unknown H(+)-coupled monocarboxylate transport system, for nicotinate in rat cerebrocortical astrocytes.

Animals↗

PubMed2005

Nitric oxide donors can enhance the intestinal transport and absorption of insulin and [Asu(1,7)]-eel calcitonin in rats.

The characteristics of three NO donors, 3-(2-hydroxy-1-(1-methylethyl)-2-nitrosohydrazino)-1-propanamine (NOC5), N-ethyl-2-(1-ethyl-2-hydroxy-2-nitrosohydrazino)-ethanamine (NOC12) and S-nitroso-N-acetyl-DL-penicillamine (SNAP) as absorption enhancers for peptide drugs were examined in rats using a modified Ussing chamber method and an in situ closed loop method. Insulin and [Asu(1,7)]-eel calcitonin (ECT) were used as a model drug to investigate the effectiveness of the tested enhancers. The NO donors significantly increased the in vitro permeability of insulin across all intestinal membranes. In general, the absorption enhancement effects of these NO donors were greater in the colon than those in the jejunum and ileum. Of these NO donors, SNAP was the most effective enhancer. Their effects were concentration-dependent over the range of 0.01 to 0.1 mM. However, 0.1 mM NO donors had almost the same effects as those at 1 mM concentration. The absorption-enhancing effects of the three NO donors were inhibited by the co-administration of 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazole-1-oxyl 3-oxide, sodium salt (carboxy-PTIO), an NO scavenger, suggesting that NO might be responsible for the efficacy of NO donors. In the in situ closed loop experiments, the three enhancers significantly improved the pharmacological availability % (PA%) of insulin in the small and large intestine. Similar results were also obtained when NO donors were added to ECT solution by an in situ closed loop method. These results suggest that NO donors possess excellent effectiveness for the use as absorption enhancers of peptide drugs and they are very effective at lower concentrations compared to the conventional enhancers.

Animals↗

PubMed2005

The effect of ezetimibe on serum lipids and lipoproteins in patients with homozygous familial hypercholesterolemia undergoing LDL-apheresis therapy.

LDL-apheresis is now commonly used as the only practical treatment for homozygous familial hypercholestreolemia (homozygous FH). However, even when applying apheresis therapy, the use of a drug or drugs is recommended to suppress the rapid rebound of cholesterol, which usually takes place after each apheresis procedure, and keep the LDL-cholesterol level within or near the optimal range for as long as possible. In this study, the usefulness of ezetimibe, a novel cholesterol-lowering drug, in enhancing the efficacy of apheresis therapy was evaluated in six Japanese patients with homozygous FH undergoing LDL-apheresis in combination with atorvastatin or simvastatin. With the exception of one patient, significant decreases in LDL-cholesterol at 2 weeks after each apheresis procedure were obtained during the period from 4 to 12 weeks of treatment, with an average reduction rate of 9.0% and a range of 4.3-12.6%. This corresponds to a suppression of rebound by approximately 36 mg/dl, from 391 to 355 mg/dl on average, in LDL-cholesterol values. Although the effect is not very strong, ezetimibe nevertheless appears to be a useful drug in combination with statins for those with homozygous FH undergoing LDL-apheresis.

Adult↗

PubMed2005

Age-related signal intensity changes in the corpus callosum: assessment with three orthogonal FLAIR images.

The presence of age-related hyperintensities of the corpus callosum has not been thoroughly evaluated. Fifty-two patients of 50 years of age or older (mean, 71 years; range, 50-87 years) were included in this study. Fluid-attenuated inversion recovery images were obtained in three orthogonal planes. Periventricular hyperintensities (PVHs) and deep white matter hyperintensities (DWMHs) were graded according to Fazekas' rating scale. Correlations between the presence of hyperintensities in the corpus callosum and age, and the grade of PVH and DWMH were statistically analyzed. PVH was categorized as grade 0 (n=4), grade 1 (n=28), grade 2 (n=10), or grade 3 (n=10). DWMH was categorized as grade 0 (n=4), grade 1 (n=25), grade 2 (n=8), or grade 3 (n=15). Hyperintensity was considered present in the corpus callosum in 31 of the 52 patients (60%). In these 31 patients, PVH was categorized as grade 1 (n=16), grade 2 (n=7), or grade 3 (n=8), while DWMH was categorized as grade 0 (n=1), grade 1 (n=10), grade 2 (n=7), or grade 3 (n=13). The presence of callosal hyperintensities was significantly correlated with age (p=0.001), and with PVH (p=0.04) and DWMH grades (p=0.004). Hyperintensities may be present in the corpus callosum with aging, and are correlated with PVH and DWMH.

Age Factors↗

PubMed2005

Carrageenans can regulate the pulmonary absorption of antiasthmatic drugs and their retention in the rat lung tissues without any membrane damage.

Effects of various viscous vehicles on pulmonary absorption of antiasthmatic drugs were examined by an in situ pulmonary absorption experiment. Theophylline and fluticasone propionate were used as antiasthmatic drugs. The serum concentration-time profile of theophylline without viscous vehicles was similar to that following the intravenous injection, indicating that pulmonary absorption of theophylline was rapid and absolute. The serum concentration of theophylline was not controlled in the presence of 5% gelatin or 2% sodium alginate. However, 1% iota-carrageenan could control and regulate the serum concentration of theophylline. In the pharmacokinetic analysis, the C(max) values of theophylline significantly decreased, and its T(max) values increased in the presence of 1% and 2% iota-carrageenan, 1% kappa-carrageenan, and 2% sodium alginate compared with the control. The MRT and MAT values of theophylline with 1% iota-carrageenan were significantly higher than those without viscous vehicles. The local concentration of theophylline in the lung at 1h after intratracheal administration increased five-fold with 1% iota-carrageenan compared with the control. On the other hand, the pulmonary absorption of fluticasone propionate was controlled and regulated in the presence of 0.5% kappa-carrageenan. Additionally, the pulmonary inflammation after the exposure of carrageenans administered to the lung was evaluated in rats. Iota- and kappa-carrageenans did not cause local serious damage and inflammation to the pulmonary tissue. Therefore, these findings indicated that the carrageenans were effective to regulate the absorption rate of antiasthmatic drugs including theophylline and fluticasone propionate.

Absorption↗

PubMed2005

Improvement of absorption enhancing effects of n-dodecyl-beta-D-maltopyranoside by its colon-specific delivery using chitosan capsules.

In general, absorption enhancing effects of various absorption enhancers were greater in the large intestine than those in the small intestinal regions. Therefore, the effectiveness of absorption enhancers is expected to be remarkably observed, if these enhancers can be delivered to the large intestine with some poorly absorbable drugs after oral administration. In this study, therefore, we examined whether chitosan capsules were effective for the colon-specific delivery of a certain absorption enhancer and can improve the absorption enhancing action of the absorption enhancer after oral administration. 5(6)-Carboxyfluorescein (CF) was used as a model drug to investigate the site-dependent effectiveness of various absorption enhancers by an in situ closed loop method. Sodium glycocholate (NaGC), n-dodecyl-beta-d-maltopyranoside (LM), sodium salicylate (NaSal) and sodium caprate (NaCap) were used as models of absorption enhancers in this study. Overall, the absorption enhancing effects of these enhancers for intestinal absorption of CF were greater in the colon than those in the jejunum and the ileum. Especially, among these enhancers tested in this study, LM showed much greater absorption enhancing effect in the colon than in the jejunum and the ileum. Therefore, LM was selected as a model absorption enhancer to examine the effect of chitosan capsules on the absorption enhancing effect of LM. When CF and LM were orally administered to rats using chitosan capsules, the plasma concentration of CF was much higher than those in other dosage forms including solution and gelatin capsules. Therefore, chitosan capsules may be useful carriers for colon-specific delivery of LM, thereby increasing its absorption enhancing effect from the intestinal membranes.

Animals↗