Effects of Different Absorption Enhancers on the Permeation of Ebiratide, an ACTH Analogue, across Intestinal Membranes

Yamamoto, Akira; Okagawa, Taishi; Kotani, Atsushi; Uchiyama, Tomomi; Shimura, Takesada; Tabata, Shigeru; Kondo, Shuji; Muranishi, Shozo

doi:10.1111/j.2042-7158.1997.tb06041.x

Cited by 42 publications

(17 citation statements)

References 24 publications

(4 reference statements)

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“…Lindmark et al (11) has reported that ampicillin suppositories containing 5% of sodium caprate caused nonspecific damage to the rectal mucosa. This result is in agreement with the report by other reporters (31)(32)(33), suggesting that it does not cause serious cytotoxicity and its effects is reversible. This is in agreement with our current investigations.…”

Section: Discussionsupporting

confidence: 83%

Enhancement of Sodium Caprate on Intestine Absorption and Antidiabetic Action of Berberine

Zhang

et al. 2010

AAPS PharmSciTech

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Abstract. Berberine, a plant alkaloid used in traditional Chinese medicine, has a wide spectrum of pharmacological actions, but the poor bioavailability limits its clinical use. The present aim was to observe the effects of sodium caprate on the intestinal absorption and antidiabetic action of berberine. The in situ, in vitro, and in vivo models were used to observe the effect of sodium caprate on the intestinal absorption of berberine. Intestinal mucosa morphology was measured to evaluate the toxic effect of sodium caprate. Diabetic model was used to evaluate antidiabetic effect of berberine coadministrated with sodium caprate. The results showed that the absorption of berberine in the small intestine was poor and that sodium caprate could significantly improve the poor absorption of berberine in the small intestine. Sodium caprate stimulated mucosal-to-serosal transport of berberine; the enhancement ratios were 2.08, 1.49, and 3.49 in the duodenum, jejunum, and ileum, respectively. After coadministration, the area under the plasma concentration-time curve of berberine was increased 28% than that in the absence of sodium caprate. Furthermore, both berberine and coadministration with sodium caprate orally could significantly decrease fasting blood glucose and improve glucose tolerance in diabetic rats (P<0.05). The hypoglycemic effect of coadministration group was remarkably stronger, and the areas under the glucose curves was decreased 22.5%, compared with berberine treatment group (P< 0.05). Morphologic analysis indicated that sodium caprate was not significantly injurious to the intestinal mucosa. The study demonstrates that sodium caprate could significantly promote the absorption of berberine in intestine and enhance its antidiabetic effect without any serious mucosal damage.

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Section: Discussionsupporting

confidence: 83%

Enhancement of Sodium Caprate on Intestine Absorption and Antidiabetic Action of Berberine

Zhang

et al. 2010

AAPS PharmSciTech

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“…The toxicity of sodium caprate has been studied in vitro at various concentrations and durations of exposure. A close examination of the data reported suggests that sodium caprate at effective concentrations in the vicinity of its critical micelle concentration (13 mM) (Cano-Cebrian et al 2005) in vitro does not affect epithelial viability (Soderholm et al 1998) and does not cause serious cytotoxicity-its effects moreover being reversible (Yamamoto et al 1997,Quan et al 1998, Chao et al 1999,Uchiyama et al 1999. This is in agreement with our current investigations.…”

Section: Histological Evaluation Of Gastrointestinal Tissuessupporting

confidence: 82%

RETRACTED: Oral delivery of low-molecular-weight heparin using sodium caprate as absorption enhancer reaches therapeutic levels

Motlekar

Srivenugopal

Wachtel

et al. 2005

Journal of Drug Targeting

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The primary objective of this study was to evaluate sodium caprate as an oral penetration enhancer for low molecular weight heparin (LMWH), ardeparin. In vitro studies using Caco-2 cell monolayer indicated that 0.0625% of sodium caprate gave approximately 2-fold enhancement of ardeparin compared to negative control with almost 100% cell survival as evaluated by MTT cytotoxicity assay. In vivo studies in rats with ardeparin (1200 IU/kg) and sodium caprate (100 mg/kg) led to a relative bioavailability of 27% with plasma anti-factor Xa levels within the therapeutic range (> 0.2 IU/ml). Moreover, under these conditions, histological examination provided evidence that there was no damage to the gastrointestinal wall. Regional permeability studies using rat intestine indicated the colon as the region of maximum permeation. These results suggest that, at the dose administered, sodium caprate acts as a relatively safe and efficient absorption enhancer in the quest for alternatives for the oral delivery of LMWH.

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“…C 10 increased the absorption of ebiratide [135], phenol red [102], and insulin [136] across rat colonic, but not jejunal epithelial mucosae (Table II). C 10 also increased paracellular permeability of a number of solutes in the colon but not in the small intestinal mucosae of rats and rabbits [137].…”

Section: [12] Intestinal Absorption Promotersmentioning

confidence: 97%

Safety and efficacy of sodium caprate in promoting oral drug absorption: from in vitro to the clinic

Maher

Leonard²,

Jacobsen

et al. 2009

Advanced Drug Delivery Reviews

197

176

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A major challenge in oral drug delivery is the development of novel dosage forms to promote absorption of poorly permeable Class III drugs across the intestinal epithelium.To date, no absorption promoter has been approved in a formulation specifically designed for oral delivery of Class III molecules. Promoters that are designated safe for human consumption have been licensed for use in a recently approved buccal insulin spray delivery system and also for many years as part of an ampicillin rectal suppository.Unlike buccal and rectal delivery, oral formulations containing absorption promoters have the additional technical hurdle whereby the promoter and payload must be coreleased in high concentrations at the small intestinal epithelium in order to generate significant but rapidly reversible increases in permeability. The most advanced promoter in the clinic is the medium chain fatty acid (MCFA), sodium caprate (C 10 ) , a compound already approved as a direct food additive. We discuss how it has evolved to a matrix tablet format suitable for administration to humans under the headings of mechanism of action at the cellular and tissue level and in vitro and in vivo efficacy and safety studies.In specific clinical examples, we review how C 10 -based formulations are being tested for oral delivery of bisphosphonates using Gastro Intestinal Permeation Enhancement Technology, GIPET® (Merrion Pharmaceuticals, Ireland) and in a related solid dose format for anti-sense oligonucleotides (ISIS Pharmaceuticals, USA).Keywords: Oral drug delivery, Sodium caprate (C 10 ), absorption promoter, drug delivery platforms, clinical trials, oral formulation, drug delivery systems.3 TJs form a barrier to the uncontrolled absorption of noxious luminal antigens (gate function), and maintain epithelial polarity (fence function) [8,9]. In general, the TJ consists of a restrictive pathway (shunt) with a sharp molecular size cut off, and a second unrestrictive pathway (small pore) that permits paracellular permeation of molecules of radii <4.0 Å [10,11]. Depending on the intestinal region, TJ pore sizes range from 6-22Å, sufficient to permit mannitol (6.7 Å) and EDTA (10.8 Å) to permeate to an extent, whereas the passage of inulin (30-40 Å) and fluorescent-dextran 4kDa (FD-4, 26 Å) is essentially impeded [12][13][14][15][16].A number of approaches have been used to promote oral delivery of Class III drugs ( Alternatively, the use of nanoparticles comprising biocompatible polymers (e.g. chitosan,polylactide-co-glycolide, starch and glucans) can protect cargoes from GI proteases, increase GI retention and promote absorption across gut associated lymphoid tissue (GALT) and to a lesser extent, enterocytes [45][46][47]. Most data on nanoparticle absorption from rodent models suggest that M cells in the follicle-associated epithelium of Peyer's patches (PP) are the favored site of uptake for particles of diameter 500nm-1000nm [45].Given the paucity of M cells in the GI tract of adults, the relevance of PP uptake remains controversial ...

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Effects of Different Absorption Enhancers on the Permeation of Ebiratide, an ACTH Analogue, across Intestinal Membranes

Cited by 42 publications

References 24 publications

Enhancement of Sodium Caprate on Intestine Absorption and Antidiabetic Action of Berberine

Enhancement of Sodium Caprate on Intestine Absorption and Antidiabetic Action of Berberine

RETRACTED: Oral delivery of low-molecular-weight heparin using sodium caprate as absorption enhancer reaches therapeutic levels

Safety and efficacy of sodium caprate in promoting oral drug absorption: from in vitro to the clinic

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