Improvement of intestinal absorption of water-soluble macromolecules by various polyamines: Intestinal mucosal toxicity and absorption-enhancing mechanism of spermine

Gao, Yang; He, Lei; Katsumi, Hidemasa; Sakane, Toshiyasu; Fujita, Takuya; Yamamoto, Akira

doi:10.1016/j.ijpharm.2007.11.061

Cited by 52 publications

(18 citation statements)

References 24 publications

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“…Spermine itself is known as a mucosal absorption-enhancer for water-soluble macromolecules. 15) However, the results in this report were related to the SP, not free spermine, because SP was stable in BALF for a few hours (data not shown).…”

mentioning

confidence: 58%

Effects of Sperminated Pullulans on the Pulmonary Absorption of Insulin

et al. 2011

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Sperminated pullulans (SP) having diŠerent molecular weights (MWs) were prepared, and the enhancing eŠect on the pulmonary absorption of insulin in rats was examined. SP acted as enhancers of insulin absorption when a 0.1％ solution was applied with insulin simultaneously and their enhancing eŠects depended on the MW of the SP; the same solutions exhibited low toxicity in the in vivo LDH leaching test. In the in vitro experiments using Calu-3 cells, tight junctionopening eŠects and a toxic eŠect of SP in the MTT assay were observed at lower concentrations compared with the in vivo experiments. A mucus layer might interfere with the interaction between SP and the cell surface and might suppress both these eŠects and toxicity. SP having a high MW will be useful for preparing safe and e‹cient formulations of peptide and protein drugs. The change in the localization of the tight junction proteins may be related to the permeation-enhancing mechanism of SP.

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confidence: 58%

Effects of Sperminated Pullulans on the Pulmonary Absorption of Insulin

et al. 2011

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“…[18][19][20][21] Excipients chosen for evaluation represent a variety of functional categories and diverse chemical structures. The excipient concentration used in this study (Table 2) was determined based on the following considerations: Disodium EDTA is widely reported to decrease the integrity of intestinal cell monolayer (Caco-2) 30 and excised intestinal epithelium, 31 so three concentrations (0.05%, 0.1%, and 1%) were chosen to cover the relevant levels of use. For all other excipients, a single concentration was studied.…”

Section: Selection Of Excipients and Determination Of Experimental Comentioning

confidence: 99%

The Effect of Commonly Used Excipients on the Epithelial Integrity of Human Cervicovaginal Tissue

Zhou

Dezzutti

et al. 2016

AIDS Research and Human Retroviruses

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Pharmaceutical excipients are widely used in vaginal drug products. The epithelial integrity of the cervicovaginal tissue is important for HIV-1 prevention. However, the effects of excipients on cervicovaginal epithelium remain unknown. This study aims at assessing the effects of vaginal product excipients on the integrity of human cervicovaginal epithelium and on a lead HIV prevention antiretroviral drug, tenofovir (TFV). In the current study, nine excipients commonly used in vaginal formulations were incubated for 6 h with excised human ectocervical tissue. The effects of the excipients were examined by measuring the transepithelial electrical resistance (TEER), epithelial morphology, paracellular/transcellular permeability, and cell viability. The efficacy of TFV for preventing HIV-1 infection in the ex vivo cultured ectocervix was also tested. We found that disodium ethyl-enediaminetetraacetate (EDTA), sorbic acid, and benzoic acid had no effect on the tissue TEER. Butylated hydroxyanisole, glycerin, propylene glycol, methylparaben, and propylparaben slightly to moderately decreased tissue TEER, whereas citric acid significantly decreased the TEER in a time-dependent manner. Tissue morphology observed post-exposure strongly correlated with TEER data; however, a less strong correlation was observed between paracellular permeability and TEER data after exposure to different excipients. In addition, treatment with EDTA, methylparaben, and propylene glycol at tested levels had no effect on the efficacy of TFV in preventing tissue HIV-1 infection. In conclusion, the combined measurements of TEER, morphology, permeability, and viability using human cervicovaginal tissue represent a clinically relevant platform for safety evaluation of excipients and formulated products for HIV-1 prevention.

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“…[7][8][9][10][11][12][13][14][15][16] Among these various chemical classes, acylated amino acids are surfactants with natural lipid-like structures and exhibit amphiphilic properties with high surface activity, as they are composed of a fatty acid and an amino acid, which are lipophilic and hydrophilic moieties respectively. 17) Because of their natural building blocks, these amino acid surfactants are regarded as "green" surfactants and are widely used in pharmaceutical, cosmetic, and food industries to replace petroleum-sourced surfactants.…”

Section: Curcuminmentioning

confidence: 99%

Improvement of the Solubility and Intestinal Absorption of Curcumin by <i>N</i>-Acyl Taurates and Elucidation of the Absorption-Enhancing Mechanisms

Kawamura

Sato

et al. 2017

Biological & Pharmaceutical Bulletin

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In this study, the effects of N-acyl taurates (NATs) on the intestinal absorption of curcumin (CUR), a water-insoluble and poorly absorbed compound, were examined in rats. Sodium methyl lauroyl taurate (LMT) and sodium methyl cocoyl taurate (CMT) were the most effective in increasing the solubility and intestinal absorption of CUR. The intestinal membrane toxicity of the NATs was also evaluated by measuring the activity of lactate dehydrogenase (LDH), a toxicity marker. NATs did not increase the activity of LDH, suggesting that they may be safely administered orally. We further elucidated the absorption-enhancing mechanisms of NATs by using Caco-2 cells. In cellular transport studies, LMT and CMT reduced the transepithelial electrical resistance value of Caco-2 cells and increased the transport of 5(6)-carboxyfluorescein and CUR. Hence, the intestinal absorption enhancement by LMT and CMT was attributed to the synergistic effect of higher solubility and greater permeability of the cell layer towards CUR in the presence of the surfactants. In summary, co-administration of CUR with either LMT or CMT is a simple and effective method to enhance oral delivery of CUR.

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Improvement of intestinal absorption of water-soluble macromolecules by various polyamines: Intestinal mucosal toxicity and absorption-enhancing mechanism of spermine

Cited by 52 publications

References 24 publications

Effects of Sperminated Pullulans on the Pulmonary Absorption of Insulin

Effects of Sperminated Pullulans on the Pulmonary Absorption of Insulin

The Effect of Commonly Used Excipients on the Epithelial Integrity of Human Cervicovaginal Tissue

Improvement of the Solubility and Intestinal Absorption of Curcumin by <i>N</i>-Acyl Taurates and Elucidation of the Absorption-Enhancing Mechanisms

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