Gastrointestinal region specific insulin absorption enhancement by Aloe vera leaf materials

Abstract

The oral administration route is still the most popular and preferred route for drug administration, but is, however, not suitable for protein and peptide drugs such as insulin, due to their poor bioavailability when administered orally. This can be attributed mainly to the unfavourable physicochemical properties of the protein and peptide drugs and the considerable barriers that the gastrointestinal tract (GIT) poses to drug absorption. In order to overcome this problem, drug absorption enhancers which act to minimise the barriers presented by the epithelial cells can be added to drug delivery systems. These absorption enhancing agents may facilitate the absorption of poorly absorbable hydrophilic and macromolecular drugs via opening tight junctions. Although it has been shown in previous studies that aloe leaf materials improve intestinal drug transport, their effect on the regional gastrointestinal absorption has not yet been investigated. The aim of this study is to determine whether the intestinal drug absorption enhancement effects of A. vera gel and whole leaf materials are region specific and to identify the region in the GIT where maximum absorption enhancement of insulin is achieved. The transport of insulin across excised pig intestinal tissues from various regions of the GIT (i.e. the duodenum, proximal jejunum, medial jejunum, distal jejunum, ileum and colon) was measured in the absence and presence of A. vera gel and whole leaf materials (0.5% w/v) using the Sweetana-Grass diffusion chamber as well as the everted sac technique. Apical-to-basolateral transport of insulin was measured over a period of 2 h at a concentration of 170 μg/ml in the diffusion apparatus, while 17 μg/ml was used in the everted sac technique due to the larger surface area available for absorption. Test solutions were prepared in Krebs Ringer bicarbonate (KRB) buffer at the pH values of 6.8 for the duodenum and 7.4 for the jejunum, ileum and colon. Analysis of the samples (200 μl) withdrawn from the acceptor chambers at 20 min intervals was conducted by means of a validated high performance liquid chromatograpy (HPLC) method. The results showed that the A. vera gel mediated a statistically significant (p < 0.05) increase in insulin transport in the duodenum, distal jejunum and colon compared to the control group in the diffusion apparatus. The A. vera whole leaf material mediated a statistically significant (p < 0.05) increase in insulin transport in the proximal jejunum compared to the control group in the diffusion apparatus. Insulin transport was enhanced statistically significantly (p < 0.05) in the ileum and colon by A. vera gel in the everted sac technique, while the A. vera whole leaf material increased the insulin transport statistically significantly (p < 0.05) only in the proximal jejunum. Insulin transport was reduced in some of the GIT regions by the A. vera gel and whole leaf materials. The increased insulin transport can possibly be explained by the opening of tight junctions as indicated by a reduction in the transepithelial electrical resistance (TEER) values, while the reduction in insulin transport can probably be explained by different interactions of the aloe materials with different intestinal tissues. The results indicated that the addition of A. vera gel and whole leaf materials had a statistically significant effect on the in vitro transport of insulin across some of the six GIT regions.