Enhancement potential of sucrose laurate (L-1695) on intestinal absorption of water-soluble high molecular weight compounds.

Published on Aug 1, 2012in Current Drug Delivery1.645
· DOI :10.2174/156720112802650699
Hiraku Onishi24
Estimated H-index: 24
Yu Imura1
Estimated H-index: 1
+ 1 AuthorsYoshiharu Machida38
Estimated H-index: 38
Purpose: The potential of sucrose fatty acid esters (SEs) to enhance intestinal absorption was investigated in order to identify their utility for the intestinal absorption of water-soluble high molecular weight compounds. Methods: Fluorescein isothiocyanate-labeled dextran (FD) with a molecular weight (MW) of 4,000 (FD-4) was used as a model compound, and several SEs were tested as absorption enhancers. After FD-4 was administered intra-duodenally at 10 % (w/v) with the non-loop method in situ in rats in the absence or presence of SEs, the plasma concentration-time profiles of FD-4 were examined. As to sucrose laurate (L-1695), the relationship between concentration and enhancement effect was investigated. In addition, the enhancement effect after dosing into the different small intestinal regions, the effect on FDs with different MWs and the influence of N-acetyl-cysteine (NAC) co-existence were examined. Results: Low watersoluble SEs exhibited slight and/or slow absorption enhancement effects, while L-1695, being highly water-soluble, had good potential to enhance the absorption rate and extent. The enhancement effect became greater as the concentration of L1695 increased. L-1695 displayed high enhancement potential in wide intestinal areas. The enhancement effect of L-1695 (10 %, w/v) depended on MWs of FDs; the mean values of the area under the plasma concentration curve from 0-120 min (AUC0-120 mins) increased by 14 and 8 times for FD-4 and FD-10 (MW 10,000), while it was hardly changed as for FD-70 (MW 70,000). The enhancement effect of L-1695 (10 %, w/v) was similar to that of sodium caprate (10 %, w/v), and was influenced to some extent by the co-existence of NAC (5 %, w/v). Conclusion: The absorption enhancement potential of SEs depended on their water-solubility. L-1695, being highly water-soluble, showed a good enhancement effect, and its absorption profiles were elucidated. This study proposes the possibility of SEs, in particular, L-1695, as intestinal absorption enhancers. As far as the present non-loop method is concerned, the intestinal damage was not observed macroscopically with the addition of L1695 at 2.5-20 % (w/v).
  • References (0)
  • Citations (6)
📖 Papers frequently viewed together
1 Citations
53 Citations
22 Citations
78% of Scinapse members use related papers. After signing in, all features are FREE.
Cited By6
#1Fiona McCartneyH-Index: 3
#2Monica RosaH-Index: 6
Last. David J. BraydenH-Index: 37
view all 3 authors...
Oral delivery of macromolecules requires permeation enhancers (PEs) adaptable to formulation. Sucrose laurate (SL) (D1216), a food grade surfactant, was assessed in Caco-2 monolayers, isolated rat intestinal tissue mucosae, and rat intestinal instillations. Accordingly, 1 mM SL increased the apparent permeability coefficient (Papp) of [14C]-mannitol and reduced transepithelial electrical resistance (TEER) across monolayers. It altered expression of the tight junction protein, ZO-1, increased pla...
1 CitationsSource
Abstract Surfactant food emulsifiers are among the most extensively used food additives. Like all authorized food additives, emulsifiers have been evaluated by risk assessors, who consider them as safe. However, there are growing concerns among scientists about their possible harmful effects on intestinal barriers and microbiota. It is also suggested that emulsifier consumption might be one of the main causes of the rising incidence of a number of diseases, such as allergic diseases, celiac dise...
#1Sam MaherH-Index: 18
#2David J. BraydenH-Index: 37
Last. Lisbeth IllumH-Index: 75
view all 4 authors...
The application of permeation enhancers (PEs) to improve transport of poorly absorbed active pharmaceutical ingredients across the intestinal epithelium is a widely tested approach. Several hundred compounds have been shown to alter the epithelial barrier, and although the research emphasis has broadened to encompass a role for nanoparticle approaches, PEs represent a key constituent of conventional oral formulations that have progressed to clinical testing. In this review, we highlight promisin...
4 CitationsSource
#1Sam Maher (RCSI: Royal College of Surgeons in Ireland)H-Index: 18
#2Randall J. Mrsny (University of Bath)H-Index: 36
Last. David J. Brayden (UCD: University College Dublin)H-Index: 37
view all 3 authors...
Intestinal permeation enhancers (PEs) are one of the most widely tested strategies to improve oral delivery of therapeutic peptides. This article assesses the intestinal permeation enhancement action of over 250 PEs that have been tested in intestinal delivery models. In depth analysis of pre-clinical data is presented for PEs as components of proprietary delivery systems that have progressed to clinical trials. Given the importance of co-presentation of sufficiently high concentrations of PE an...
82 CitationsSource
#1Ying Li (SPU: Shenyang Pharmaceutical University)H-Index: 1
#2Jinfeng Li (SPU: Shenyang Pharmaceutical University)H-Index: 6
Last. Shirui Mao (SPU: Shenyang Pharmaceutical University)H-Index: 25
view all 5 authors...
AbstractObjective: To explore the potential of non-ionic surfactants as novel intranasal absorption enhancers.Methods: Taking sumatriptan succinate (SMS) as a model drug, influence of different non-ionic surfactants, including laurate sucrose ester (SE), cremophor EL and poloxamer 188, on the intranasal absorption of SMS was investigated using an in situ nasal perfusion technique in rats. Ciliotoxicity of the non-ionic surfactants was evaluated using an in situ toad palate model. In vivo behavio...
8 CitationsSource
#1Loránd Kiss (MTA: Hungarian Academy of Sciences)H-Index: 23
#2Éva HellingerH-Index: 6
Last. Mária A. Deli (MTA: Hungarian Academy of Sciences)H-Index: 36
view all 14 authors...
ABSTRACT Sucrose fatty acid esters are increasingly used as excipients in pharmaceutical products, but few data are available on their toxicity profile, mode of action, and efficacy on intestinal epithelial models. Three water‐soluble sucrose esters, palmitate (P‐1695), myristate (M‐1695), laurate (D‐1216), and two reference absorption enhancers, Tween 80 and Cremophor RH40, were tested on Caco‐2 cells. Caco‐2 monolayers formed a good barrier as reflected by high transepithelial resistance and p...
18 CitationsSource
Surfactants used in pharmaceutical products have several advantageous properties; they improve drug absorption and dissolution, and protect active molecules. However, adverse effects are also observed during the application of different surface active agents which necessitates the investigation of registered surfactants and novel absorption enhancer candidates. Cremophor RH40 and EL are widely used excipients in oral and intravenous drug formulations. Studies indicate that Cremophors, especially...