Enhancement Potential of Sucrose Laurate (L-1695) on Intestinal Absorption of Water-Soluble High Molecular Weight Compounds

Hiraku      Onishi; Yu      Imura; Minoru      Uchida; Yoshiharu      Machida

Abstract

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).

Keywords: Fluorescein isothiocyanate-labeled dextran, intestinal absorption enhancement, non-loop method, sucrose fatty acid ester, sucrose laurate, biodegradable architecture, hydrophilic substances, glycoproteins.