Amino Acids Protect Epithelial Cells From Local Toxicity by Absorption Enhancer, Sodium Laurate

Yata, Takashi; Endo, Yoko; Sone, Miki; Ogawara, Ken Ichi; Higaki, Kazutaka; Kimura, Takeshi

doi:10.1002/jps.1097

Cited by 23 publications

(27 citation statements)

References 39 publications

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“…Keys: ϫ, Control suppository; ᭺, suppository f (20 mg C12); ᭹, suppository j (20 mg C12ϩ30 mg Tau); ᭝, suppository a (15 mg C10); ᭡, suppository b (25 mg C10); ٗ, suppository e (10 mg C12); , suppository h (10 mg C12ϩ30 mg Tau). Table 4 evidenced, 26,27) which might be attributed to the opening of tight junction and the enhancement of membrane fluidity. 26) Although we previously reported that the addition of Tau attenuated the enhancing effect of C12, 25,30) Tau hardly decreased the absorption improving effect of C12 in the case of the suppositories containing 20-mg C12, when compared with the suppositories containing 10-mg C12 (Fig.…”

Section: Resultsmentioning

confidence: 94%

“…[21][22][23] We have found that C12, a mediumchain fatty acid salt, is a promising absorption enhancer and better than C10 in terms of the absorption improving ability, 24) and that Tau has the most effective cytoprotective activity among amino acids examined. 25) Cytoprotective action by Tau has been evidenced by both biochemical [25][26][27] and histopathological 25) approaches and it has been partially related with the suppression of intracellular Ca 2ϩ level elevated by C12 and the inhibition of histamine release induced by C12. L-Glutamine (L-Gln) also has the cytoprotective action, which is partially attributed to the induction of heat-shock protein 70 (HSP70), 27) a factor protecting cells from injuries caused by several kinds of stresses.…”

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confidence: 99%

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Optimization of Suppository Preparation Containing Sodium Laurate and Taurine That Can Safely Improve Rectal Absorption of Rebamipide

Miyake

Minami

Oka

et al. 2006

Biological & Pharmaceutical Bulletin

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Drug absorption from gastrointestinal tract is mainly influenced by solubility and permeability. As a technique of the improvement of solubility, micronization, amorphousization and the addition of surfactant such as Tween 80 and Captisol ® are well known. As for the improvement of permeability, the use of absorption enhancers is well known, [1][2][3][4][5][6][7][8][9][10][11] but the practical use of them has been very limited 12,13) because of the potential local toxicity to gastrointestinal mucosa. 2,4) In order to develop the safe formulation that can improve the absorption of drugs categorized into BCS Class IV such as rebamipide, [14][15][16][17][18][19][20] we have compared the suppository that contains sodium laurate (C12) as an absorption enhancer and taurine (Tau) as a cytoprotective adjuvant with the commercial suppository that contains sodium caprate (C10) as an absorption enhancer. [21][22][23] We have found that C12, a mediumchain fatty acid salt, is a promising absorption enhancer and better than C10 in terms of the absorption improving ability, 24) and that Tau has the most effective cytoprotective activity among amino acids examined. 25) Cytoprotective action by Tau has been evidenced by both biochemical [25][26][27] and histopathological 25) approaches and it has been partially related with the suppression of intracellular Ca 2ϩ level elevated by C12 and the inhibition of histamine release induced by C12. L-Glutamine (L-Gln) also has the cytoprotective action, which is partially attributed to the induction of heat-shock protein 70 (HSP70), 27) a factor protecting cells from injuries caused by several kinds of stresses. 28,29) Furthermore, basic studies for suppository were performed in rats by administering the fatty or water-soluble base preparation containing rebamipide, C12 and Tau or L-Gln into rats. The combinatorial use of them, especially for the fatty base (FB) suppository, has been evidenced to be promising in terms of both improvement of bioavailability and safety to rat rectal mucosa.30) However, the success in the scaling-up study must be necessary for developing the formulation available for human use.In the present study, we have, therefore, performed the scaling-up study of animal and formulation size using FB suppositories of rebamipide and have compared our new preparations with the commercial suppository containing C10 (15 or 25 mg) in terms of the drug dissolution, absorption improvement and safety to the rectal mucosa of rabbits. MATERIALS AND METHODSMaterials C12, C10 and Tau were purchased from Tokyo Chemical Industry Co. (Tokyo, Japan). Hydroxypropyl methylcellulose (HPMC) TC-5E (HPMC 2910) was purchased from Shin-etsu Kagaku Co. (Tokyo). Witepsol ® H-15 was obtained from Mitsuba Boueki Co. Ltd. (Tokyo). Rebamipide and OPC-12853, an internal standard, were obtained from Otsuka Pharmaceutical Co. Ltd. (Tokushima, Japan). All other reagents were analytical grade commercial products.Animals Male Japan-White rabbits (Kitayama Labes, Ina, Japan), maintained at 23°C and 60% hum...

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Section: Resultsmentioning

confidence: 94%

mentioning

confidence: 99%

Optimization of Suppository Preparation Containing Sodium Laurate and Taurine That Can Safely Improve Rectal Absorption of Rebamipide

Miyake

Minami

Oka

et al. 2006

Biological & Pharmaceutical Bulletin

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“…Studies in an in situ colon loop model showed that markers of local toxicity in the colon increased upon sodium laurate exposure (10 mM), i.e. phospholipids, total protein and lactate dehydrogenase (Yata et al, 2001). Furthermore, sodium laurate seems to increase the intracellular concentration of Ca 2+ in rat intestinal epithelial cells and to cause a dosedependent increase in the release of histamine from the cells (Endo et al, 2002).…”

Section: Effects On Absorption Of Other Compoundsmentioning

confidence: 99%

“…This local toxicity seems to be the reason why only sodium caprate is used as an absorption-enhancer in drug products (Yata et al, 2001). Amino acids have however been shown to protect epithelial cells from local toxicity caused by sodium laurate, while the enhancement of drug absorption is maintained (Takayama et al, 2009;Yata et al, 2001).…”

Section: Effects On Absorption Of Other Compoundsmentioning

confidence: 99%

Scientific Opinion on the safety of sucrose esters of fatty acids prepared from vinyl esters of fatty acids and on the extension of use of sucrose esters of fatty acids in flavourings

2010

EFS2

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The Panel on Food Additives and Nutrient Sources added to Food provides a scientific opinion on the safety of sucrose esters of fatty acids produced by a new manufacturing method from sucrose and vinyl esters of fatty acids, and an evaluation of the extension of the use of this additive to flavoured fruit beverages. In 2004 EFSA established a group ADI of 40 mg/kg bw/day for sucrose esters of fatty acids, however this evaluation did not consider sucrose esters of lauric acid. The Panel considers that although the toxicological data on the sucrose ester of lauric acid are limited, they do not give rise to concerns since lauric acid is a natural constituent of a number of foods. The new manufacturing method results in residues of vinyl esters of fatty acids of <10-111 mg/kg and acetaldehyde of 20-48 mg/kg in the sucrose esters of fatty acids. p-Methoxyphenol was undetectable. The vinyl portion of the vinyl ester instantly tautomerises to acetaldehyde in the gastrointestinal tract. The Panel concludes that the additional average exposure of 1.4 µg acetaldehyde/kg bw/day resulting from the use of sucrose esters of fatty acids as a food additive would be negligible compared to the exposure from food and endogenous formation and not of safety concern. The Panel also concludes that since pmethoxyphenol was undetectable, this potential residue is not of safety concern. The Panel therefore concludes that sucrose esters of fatty acids produced by the new manufacturing method do not present any safety concern provided the overall exposure is within the ADI of 40 mg/kg bw/day. The Panel notes that the current intake of sucrose esters of fatty acids is high and for some individuals above the ADI but that an additional intake from fruit beverages only seems to contribute to a few percent of the ADI. KEY WORDSSucrose monoesters of fatty acids, manufacturing method, vinyl esters of fatty acids, acetaldehyde, E473, food additive, emulsifier, stabiliser

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“…The tight intercellular junctions between the epithelial cells restrict the absorption of drugs and control the access of potential antigens and pathogens from the lumen to submucosa (De Magistris 2006). Efforts to design novel formulations to breach the mucosal barrier for efficient antigen presentation to the M cells or their transport to draining lymph nodes either by lamina propria dendritic cells or by lymphatics (Rescigno et al 2001), and to enhance the absorption of poorly soluble and poorly absorbable drugs have been increasing recently (Messing et al 1999;Aungst 2000;Yata et al 2001;Endo et al 2002;Ohtake et al 2002;Miyake et al 2003Miyake et al , 2004Miyake et al , 2006Li et al 2005;Seki et al 2005).…”

Section: Introductionmentioning

confidence: 99%

Transport of Surface Engineered Polyamidoamine (PAMAM) Dendrimers Across IPEC-J2 Cell Monolayers

Pisal¹,

Yellepeddi²,

Kumar³

et al. 2008

Drug Delivery

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The aim of our study was to prepare arginine-and ornithineconjugated Polyamidoamine (PAMAM) dendrimers and study their permeability across IPEC-J2 cell monolayers, a new intestinal cell line model for drug absorption studies. Arginine and ornithine were conjugated to the amine terminals of the PAMAM G4 dendrimers by Fmoc synthesis. The apical-to-basolateral (AB) and basolateral-to-apical (BA) apparent permeability coefficients (P app ) for the PAMAM dendrimers increased by conjugating the dendrimers with both of these polyamines. The enhancement in permeability was dependent on the dendrimer concentration and duration of incubation. Correlation between monolayer permeability and the decrease in transepithelial electrical resistance (TEER) with the PAMAM dendrimers and the polyamine-conjugated dendrimers suggests that paracellular transport is one of the mechanisms of transport across the epithelial cells. Cytotoxicity of these surface-modified dendrimers was evaluated in IPEC-J2 cells by MTT (methylthiazoletetrazolium) assay. Arginine-conjugated dendrimers were insignificantly more toxic than PAMAM dendrimer as well as ornithine-conjugated dendrimers. Though investigations on the possible involvement of other transport mechanisms are in progress, results of the present study suggest the potential of dendrimer-polyamine conjugates as the carriers for antigen/drug delivery through the oral mucosa.

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Amino Acids Protect Epithelial Cells From Local Toxicity by Absorption Enhancer, Sodium Laurate

Cited by 23 publications

References 39 publications

Optimization of Suppository Preparation Containing Sodium Laurate and Taurine That Can Safely Improve Rectal Absorption of Rebamipide

Optimization of Suppository Preparation Containing Sodium Laurate and Taurine That Can Safely Improve Rectal Absorption of Rebamipide

Scientific Opinion on the safety of sucrose esters of fatty acids prepared from vinyl esters of fatty acids and on the extension of use of sucrose esters of fatty acids in flavourings

Transport of Surface Engineered Polyamidoamine (PAMAM) Dendrimers Across IPEC-J2 Cell Monolayers

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